RESUMEN

AIM: This study sought to evaluate the effects of LDT409, a pan-PPAR partial agonist obtained from the main industrial waste from cashew nut processing, on hepatic remodeling, highlighting energy metabolism and endoplasmic reticulum (ER) stress in high-fructose-fed mice. METHODS: Male C57BL/6 mice received a control diet (C) or a high-fructose diet (HFRU) for ten weeks. Then, a five-week treatment started: C, C-LDT409, HFRU, and HFRU-LDT409. The LDT409 (40 mg/kg of body weight) was mixed with the diets. RESULTS: The HFRU diet caused insulin resistance and endoplasmic reticulum (ER) stress. High Pparg and decreased Ppara expression increased steatosis and pro-fibrogenic gene expression in livers of HFRU-fed mice. Suppressed lipogenic factors, orchestrated by PPAR-gamma, and mitigated ER stress concomitant with the increase in beta-oxidation driven by PPAR-alpha mediated the LDT409 beneficial effects. CONCLUSIONS: LDT409 may represent a potential low-cost approach to treat metabolic dysfunction-associated steatotic liver disease, which does not currently have a specific treatment.

Asunto(s)

Estrés del Retículo Endoplásmico , Fructosa , Ratones Endogámicos C57BL , Animales , Masculino , Fructosa/efectos adversos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Hígado Graso/patología , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Resistencia a la Insulina , Receptores Activados del Proliferador del Peroxisoma/agonistas , Receptores Activados del Proliferador del Peroxisoma/metabolismo , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR alfa/genética , PPAR gamma/agonistas , PPAR gamma/metabolismo , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/patología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología

RESUMEN

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.

Asunto(s)

Biotina , Restricción Calórica , Suplementos Dietéticos , Retardo del Crecimiento Fetal , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Embarazo , Ratas , Restricción Calórica/métodos , Biotina/administración & dosificación , Biotina/farmacología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Retardo del Crecimiento Fetal/prevención & control , Retardo del Crecimiento Fetal/etiología , Resistencia a la Insulina , Modelos Animales de Enfermedad , Síndrome Metabólico/prevención & control , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Fructosa/efectos adversos , Factores de Riesgo Cardiometabólico , Peso Corporal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos

RESUMEN

The consumption of a high-fat high-fructose diet partly resemble the western dietary patterns, which is closely associated with excessive body adiposity and metabolic disorders, such as obesity and type 2 diabetes. Moreover, this unhealthy regime produces unfavourable changes on the faecal microbiota, potentially interfering with microorganisms postbiotic function, such as spermidine, a natural polyamine that has been involved in the control of weight gain. The study aimed to analyse the repercussions of spermidine supplementation on somatic measurements, metabolic markers, and the faecal microbiota profile of rats fed a diet rich in fat and fructose. Indeed, Wistar males with oral administration of spermidine (20 mg/kg/day) for 6 weeks were evaluated for food and energy intake, biochemical markers, and faecal microbiota signatures. The daily use of spermidine decreased weight gain ( P < 0.01), reduced feed efficiency ( P < 0.01), and attenuated visceral fat deposition ( P < 0.01), although no effect on energy intake, hepatic weight, triglyceride and glucose index and atherogenic indexes. Similarly, the consumption of spermidine partially restored the presence of microbial species, notably Akkermansia muciniphila. Elevated concentrations of this species were linked to a decrease in triglycerides ( P = 0.04), indicating that the supplementation of spermidine might contribute to managing energy fuel homeostasis in association with an obesogenic diet.

Asunto(s)

Dieta Alta en Grasa , Heces , Fructosa , Microbioma Gastrointestinal , Ratas Wistar , Espermidina , Animales , Espermidina/farmacología , Masculino , Dieta Alta en Grasa/efectos adversos , Fructosa/efectos adversos , Fructosa/administración & dosificación , Ratas , Microbioma Gastrointestinal/efectos de los fármacos , Heces/microbiología , Obesidad/microbiología , Aumento de Peso/efectos de los fármacos , Suplementos Dietéticos

RESUMEN

This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.

Asunto(s)

Fructosa , Hiperalgesia , Ratas Wistar , Animales , Fructosa/efectos adversos , Fructosa/administración & dosificación , Masculino , Hiperalgesia/metabolismo , Ratas , Inflamación/metabolismo , Inflamación/inducido químicamente , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Carragenina , Dinoprostona/metabolismo , Dinoprostona/sangre , Edema/inducido químicamente , Resistencia a la Insulina/fisiología , Lipopolisacáridos/toxicidad , Modelos Animales de Enfermedad

RESUMEN

Several models of mice-fed high-fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high-fat diet and CCl4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high-fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl4). The animals fed with HFD+CCl4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl4 group, compared with SD and HFD groups. Also, CCl4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of ∼2 times in macrophage activity, ∼6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL-1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.

Asunto(s)

Tetracloruro de Carbono , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hígado , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Triglicéridos/sangre , Triglicéridos/metabolismo , Fructosa/efectos adversos

RESUMEN

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Asunto(s)

Diabetes Mellitus Tipo 2 , Obesidad Infantil , Niño , Adulto , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/etiología , Obesidad Infantil/prevención & control , Tejido Adiposo , Tejido Adiposo Blanco , Fructosa/efectos adversos

RESUMEN

Consumption of foods with fiber and compounds can promote gastrointestinal health and reduce obesity complications. Therefore, treatment with common bean leaves (BL) against obesity was evaluated in mice with a high-fat and high-fructose diet (HFFD) for 14 weeks. The bromatological and phytochemical characterization of BL were determined. Afterwards, the animals were supplemented with BL (10%) or a standard diet (SD) as a strategy to encourage a healthy diet for 12 additional weeks. Changes in body composition, lipid profile, and intestinal integrity were analyzed. The characterization of BL stood out for its content of 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The visceral adipose tissue (VAT) decreased in the BL group by 52% compared to the HFFD group. Additionally, triglyceride levels were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the 1.77-fold higher fecal lipid excretion in the BL consumption group compared to the HFFD group and the inhibition of pancreatic lipase by 29%. Furthermore, BL supplementation reduced the serum levels of IL-6 (4.4-fold) and FITC-dextran by 50% compared with those in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

Asunto(s)

Dieta Alta en Grasa , Fructosa , Ratones , Animales , Fructosa/efectos adversos , Fructosa/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Lípidos , Ingestión de Alimentos

RESUMEN

Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.

Asunto(s)

Fructosa , Efectos Tardíos de la Exposición Prenatal , Embarazo , Ratones , Masculino , Femenino , Animales , Humanos , Fructosa/efectos adversos , Obesidad , Peso Corporal , Adiposidad , Lactancia , Efectos Tardíos de la Exposición Prenatal/metabolismo

RESUMEN

Metabolic syndrome (MS) is a disorder that increasingly affects the world population, mainly because of changes in lifestyle and dietary habits. In this regard, both physical exercise and caffeine are low-cost and easily accessible therapies that separately have shown positive effects against metabolic disorders. Therefore, we hypothesized that physical exercise combined with caffeine could have a synergistic effect in the treatment of MS, risk factors, and cognitive deficits. Animals were divided into 8 groups and received fructose (15% w/v) or vehicle for 10 weeks. Swimming training and caffeine (6 mg/kg) started 4 weeks after fructose administration. Trained animals presented decreased body weight and visceral fat mass and increased soleus weight compared with untrained fructose-treated animals. Caffeine supplementation also prevented the gain of visceral fat mass induced by fructose. Furthermore, both treatments reversed fructose-induced decrease in glucose clearance over time and fructose-induced increase in 4-hydroxynonenal and nuclear factor-κB immunoreactivity. Physical training also improved the lipidic profile in fructose-treated animals (high-density lipoprotein, low-density lipoprotein, and triglycerides), improved short-term, long-term, and localization memory, and reversed the fructose-induced deficit in short-term memory. Physical training also increased nuclear factor erythroid 2-related factor 2 immunoreactivity per se. Considering that physical training and caffeine reversed some of the damages induced by fructose it is plausible to consider these treatments as alternative, nonpharmacological, and low-cost therapies to help reduce MS-associated risk factors; however, combined treatments did not show additive effects as hypothesized.

Asunto(s)

Síndrome Metabólico , Ratas , Animales , Síndrome Metabólico/prevención & control , Cafeína/farmacología , FN-kappa B , Natación , Ratas Wistar , Suplementos Dietéticos , Cognición , Fructosa/efectos adversos

RESUMEN

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Asunto(s)

Enfermedades Cardiovasculares , Resistencia a la Insulina , Ratas , Animales , Presión Arterial , Barorreflejo , Fructosa/efectos adversos , Ratas Wistar , Glucemia/metabolismo , Presión Sanguínea

RESUMEN

The rising fructose intake in sugar-sweetened beverages and ultra-processed foods relates to the high incidence of nonalcoholic fatty liver disease. This study aimed to examine the effects of long-term high-fructose diet intake (for 16 or 20 weeks) on progressive hepatic damage, focusing on the endoplasmic reticulum stress markers and fibrogenesis as possible triggers of liver fibrosis. Forty 3-month-old male C57BL/6J mice were randomly divided into four nutritional groups: C16 (control diet for 16 weeks), C20 (control diet for 20 weeks), HFRU16 (high-fructose diet for 16 weeks), and HFRU20 (high-fructose diet for 20 weeks). Both HFRU groups showed oral glucose intolerance and insulin resistance, but only the HFRU20 group exhibited increased inflammation. The increased lipogenic and endoplasmic reticulum stress markers triggered hepatic fibrogenesis. Hence, time-dependent perivascular fibrosis with positive immunostaining for alpha-smooth muscle actin and reelin in HFRU mice was observed, ensuring fibrosis development in this mouse model. Our study showed time-dependent and progressive damage on hepatic cytoarchitecture, with maximization of hepatic steatosis without overweight in HFRU20 mice. ER stress and liver inflammation could mediate hepatic stellate cell activation and fibrogenesis, emerging as targets to prevent NAFLD progression and fibrosis onset in this dietary model.

Asunto(s)

Fructosa , Enfermedad del Hígado Graso no Alcohólico , Masculino , Ratones , Animales , Fructosa/efectos adversos , Ratones Endogámicos C57BL , Hígado , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Fibrosis , Inflamación/complicaciones , Estrés del Retículo Endoplásmico

RESUMEN

Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra-processed foods and beverages. Consumption of fructose-sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro-inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3-PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams' MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

Asunto(s)

Enfermedades Neuroinflamatorias , Efectos Tardíos de la Exposición Prenatal , Ratas , Animales , Masculino , Femenino , Humanos , Ratas Wistar , Peroxidación de Lípido , Lactancia/metabolismo , Fructosa/efectos adversos , Fructosa/metabolismo , Agua/farmacología , Efectos Tardíos de la Exposición Prenatal/metabolismo

RESUMEN

BACKGROUND: Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. OBJECTIVE: This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. METHODS: Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. RESULTS: Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. CONCLUSION: Fructose consumption alters BAs associated with CVD risk factors.

---

FUNDAMENTO: As doenças cardiovasculares (DCV) são a principal causa de mortalidade do mundo, e um de seus fatores de risco são os hábitos alimentares não saudáveis, tais como, o alto consumo de frutose. As aminas biogênicas (ABs) realizam funções importantes no corpo humano. Entretanto, o efeito do consumo de frutose nos níveis das ABs ainda não está claro, bem como a associação entre estes e os fatores de risco da DCV. OBJETIVO: Este estudo teve o objetivo de estabelecer a associação entre os níveis de ABs e os fatores de risco de DCV em animais que consumiram frutose. MÉTODOS: Ratos Wistar machos receberam ração convencional (n=8) ou ração convencional + frutose na água de beber (30%) (n=8) durante 24 semanas. Ao final, foram analisados os parâmetros nutricionais e da síndrome metabólica (SM) e os níveis plasmáticos das ABs. Foi adotado um nível de significância de 5%. RESULTADOS: O consumo de frutose levou à SM, reduziu os níveis de triptofano e 5-hidroxitriptofano e aumentou a histamina. Os níveis de triptofano, histamina e dopamina apresentaram correlação com parâmetros de síndrome metabólica. CONCLUSÃO: O consumo de frutose altera as ABs associadas a fatores de risco de doenças cardiovasculares.

Asunto(s)

Enfermedades Cardiovasculares , Síndrome Metabólico , Humanos , Ratas , Animales , Masculino , Ratas Wistar , Histamina , Enfermedades Cardiovasculares/etiología , Síndrome Metabólico/etiología , Triptófano , Aminas Biogénicas , Factores de Riesgo , Fructosa/efectos adversos

RESUMEN

Excessive fructose consumption is associated with the incidence of obesity and systemic inflammation, resulting in increased oxidative damage and failure to the function of brain structures. Thus, we hypothesized that fructose consumption will significantly increase inflammation, oxidative damage, and mitochondrial dysfunction in the mouse brain and, consequently, memory damage. The effects of different fructose concentrations on inflammatory and biochemical parameters in the mouse brain were evaluated. Male Swiss mice were randomized into four groups: control, with exclusive water intake, 5%, 10%, and 20% fructose group. The 10% and 20% fructose groups showed an increase in epididymal fat, in addition to higher food consumption. Inflammatory markers were increased in epididymal fat and in some brain structures. In the evaluation of oxidative damage, it was possible to observe significant increases in the hypothalamus, prefrontal cortex, and hippocampus. In the epididymal fat and in the prefrontal cortex, there was a decrease in the activity of the mitochondrial respiratory chain complexes and an increase in the striatum. Furthermore, short memory was impaired in the 10% and 20% groups but not long memory. In conclusion, excess fructose consumption can cause fat accumulation, inflammation, oxidative damage, and mitochondrial dysfunction, which can damage brain structures and consequently memory.

Asunto(s)

Fructosa , Obesidad , Ratones , Masculino , Animales , Fructosa/efectos adversos , Estrés Oxidativo , Inflamación , Encéfalo

RESUMEN

Objective: This study aimed to evaluate the differential role of a high-fat diet (HF) or high-fructose diet (HFRU) on white adipose tissue and brown adipose tissue remodeling in C57BL/6 mice.Methods: The animals were randomly assigned to receive HF (50% of energy as lipids), HFRU (50% of energy as fructose), or a control diet (C, 10% of energy as lipids) for 12 weeks. Results: The HF group became overweight from the 7th week onwards, but both HF and HFRU groups showed hyperinsulinemia, oral glucose intolerance, and adverse adipose tissue remodeling. HF and HFRU groups showed interscapular brown adipose tissue whitening, tough the reduced QA [nuclei] suggested maximized brown adipocyte dysfunction due to the HFRU diet. In contrast, HF and HFRU diets exerted similar effects upon subcutaneous white adipocytes, with a similar average cross-sectional area. Immunohistochemistry confirmed the whitening enhancement with reduced UCP1 immunodensity in the HFRU group. Conclusion: In conclusion, HF and HFRU diets had indistinguishable effects upon white adipocyte morphology, but the HFRU diet provoked a more pronounced whitening than the HF diet after a 12-week protocol. These results point to the silent and harmful impact that excessive fructose has upon the metabolism of lean mice.

Asunto(s)

Adipocitos Blancos , Dieta Alta en Grasa , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Adipocitos Blancos/metabolismo , Adipocitos Marrones/metabolismo , Ratones Endogámicos C57BL , Obesidad/etiología , Hipertrofia/inducido químicamente , Fructosa/efectos adversos , Lípidos

RESUMEN

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

Asunto(s)

Fructosa , Estrés Oxidativo , Ratas , Femenino , Animales , Fructosa/efectos adversos , Inflamación/metabolismo , Dieta Alta en Grasa/efectos adversos , Peso Corporal , Hipocampo/metabolismo , Hormonas/metabolismo , Hormonas/farmacología

RESUMEN

Both periodontal disease (PD) and metabolic syndrome (MS) represent disorders of concern worldwide. Current evidence indicates that PD and MS might negatively influence each other, increasing the risk for cardiovascular diseases (CVD), via mutual inflammatory pathways. A failure of the inflammation resolution mechanisms is crucial for these comorbidities. Fish oil-derived omega-3 has been linked with resolution-driven responses in different pathological conditions during the last years. This study evaluated the impacts of omega-3 supplementation in a rat model combining ligature-induced PD and 10% fructose intake-elicited MS. Our main findings show that 10% fructose ingestion led to an elevation of Lee index and white adipose tissue (WAT) weight, along with hepatic alterations, accompanied by an increase of leptin, and a decrement of adiponectin serum amounts, regardless of PD induction. Noteworthy, the co-induction of PD and MS resulted in higher levels of glycemia and triglycerides, being this latter effect lessened by omega-3 supplementation. In this case, the beneficial effects of omega-3 might be associated with its ability to recover the decline of serum adiponectin levels in rats with PD plus MS. As expected, PD induction led to alveolar bone loss, independent of MS induction. However, the supplementation with omega-3 restored alveolar bone in PD control animals, but not in the rats with PD combined with MS. Our study extends the knowledge about PD and MS as comorbidities, showing novel effects of omega-3 supplementation in this context.

Asunto(s)

Ácidos Grasos Omega-3 , Síndrome Metabólico , Enfermedades Periodontales , Periodontitis , Ratas , Animales , Síndrome Metabólico/tratamiento farmacológico , Adiponectina , Fructosa/efectos adversos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Periodontitis/metabolismo

RESUMEN

Background: High consumption of carbohydrates can trigger metabolic and inflammatory disorders in the body. Thus, the aim of this study was to evaluate the effect of fiber supplementation on inflammation and hepatic steatosis in mice fed high-carbohydrate diets. Methods: Swiss male mice were distributed into two control groups and two experimental groups that received isocaloric diet rich in starch (55%) or rich in fructose (55%). In the last 4 weeks of the experiment, the animals received 5% fructo-oligosaccharide (FOS) supplementation via gavage, or water in the control groups. After 16 weeks, biochemical analyses, inflammatory cytokines, and histology of the liver of the animals were performed. Results: The animals that received fructose had higher weight at the end of the experiment as well as liver weight, consumed more feed, had higher levels of tumor necrosis factor (TNF) and monocyte chemoattractant protein-1 (MCP-1), and a higher degree of hepatic steatosis when compared with the animals that received starch. However, the animals that received starch showed a higher inflammatory process. FOS supplementation was efficient in reducing liver weight and hepatic steatosis degree in animals fed with fructose diet but showed more degeneration of liver tissue and high levels of inflammatory cytokines. FOS reduced the levels of urea and total cholesterol in the starch-fed animals. Conclusions: Diets rich in carbohydrates such as starch and fructose cause deleterious effects in animals, and fiber supplementation can bring beneficial effects.

Asunto(s)

Carbohidratos de la Dieta , Hígado Graso , Ratones , Masculino , Animales , Carbohidratos de la Dieta/efectos adversos , Hígado Graso/prevención & control , Hígado/metabolismo , Inflamación/complicaciones , Almidón/metabolismo , Dieta , Suplementos Dietéticos , Fructosa/efectos adversos , Fructosa/metabolismo

RESUMEN

In the modern diet, excessive fructose intake (>50 g/day) had been driven by the increase, in recent decades, of the consumption of sugar-sweetened beverages. This phenomenon has dramatically increased within the Caribbean and Latin American regions. Epidemiological studies show that chronic high intake of fructose related to sugar-sweetened beverages increases the risk of developing several non-communicable diseases, such as chronic obstructive pulmonary disease and asthma, and may also contribute to the exacerbation of lung diseases, such as COVID-19. Evidence supports several mechanisms­such as dysregulation of the renin−angiotensin system, increased uric acid production, induction of aldose reductase activity, production of advanced glycation end-products, and activation of the mTORC1 pathway­that can be implicated in lung damage. This review addresses how these pathophysiologic and molecular mechanisms may explain the lung damage resulting from high intake of fructose.

Asunto(s)

Fructosa , Enfermedades Pulmonares , Aldehído Reductasa , Fructosa/efectos adversos , Humanos , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/fisiopatología , Diana Mecanicista del Complejo 1 de la Rapamicina , Edulcorantes/efectos adversos , Ácido Úrico

RESUMEN

High-fructose diet is associated with an increased risk of dyslipidemia, metabolic syndrome, and the development of non-alcoholic fatty liver disease (NAFLD) through chronic inflammation. The present study aimed to elucidate the potential benefit of daily consumption of Smallanthus sonchifolius (yacon) roots, rich in fructooligosaccharides (FOS), on the progression to liver fibrosis, in a rat model of NAFLD induced by a high-fructose diet. Male Wistar rats were fed a standard diet (CD, n = 6) or a standard diet plus 10% fructose solution (FD; n = 18). After 20 weeks, FD rats were randomly separated into the following groups (n = 6, each): FD; FD treated with yacon flour (340 mg FOS/body weight; FD + Y) and FD treated with fenofibrate (30 mg/kg body weight; FD + F), for 16 weeks. Daily intake of yacon flour significantly reduced body weight gain, plasma lipid levels, transaminase activities, and improved systemic insulin response in FD rats. In the liver, yacon treatment decreased fructose-induced steatosis and inflammation, and reduced total collagen deposition (64%). Also, yacon decreased TGF-ß1 mRNA expression (78%), followed by decreased nuclear localization of p-Smad2/3 in liver tissue. Yacon significantly reduced the expression of α-smooth muscle actin (α-SMA), Col1α1, and Col3α1 mRNAs (85, 44, and 47%, respectively), inhibiting the activation of resident hepatic stellate cells (HSCs). These results suggested that yacon roots have the potential to ameliorate liver damage caused by long-term consumption of a high-fructose diet, being a promising nutritional strategy in NAFLD management.

Asunto(s)

Asteraceae , Fenofibrato , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratas , Actinas/metabolismo , Dieta , Fenofibrato/metabolismo , Fructosa/efectos adversos , Inflamación , Insulina/metabolismo , Lípidos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Ratas Wistar , ARN Mensajero , Transaminasas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Aumento de Peso