RESUMO
N-carbamylglutamate (NCG) is postulated to improve fetal growth in nutrient-restricted gestations when supplemented from day 35 to 110 of gestation, but the effects of supplementation from 100 days of gestation to birth have not been evaluated. The aim of this study was to evaluate the effect of oral NCG supplementation from 100 days of gestation (dga) to term in naturally nutrient-restricted grazing twin-bearing ewes, on the maternal body weight (BW), body condition score (BCS), placental morphology, fetal body and organ weights and blood biochemistry and antioxidant status in the ewe and fetuses. Eighteen twin-bearing ewes maintained under grazing management were randomly allocated to either a treatment group (NCG; n = 10), orally dosed once daily with 60 mg/kg of NCG from day 100 until 140 dga, or an unsupplemented control group (CON; n = 8). At 140 dga, blood gases, redox status, maternal and fetal plasma and fetal biometrics were obtained after caesarian section. The serum concentration of NCG was increased 15-fold in the NCG ewes compared to the CON. No major effects on dam or fetal body weight nor on blood biochemistry or antioxidant parameters were observed. These results indicate that NCG supplementation in mid-to-late gestation to grazing ewes was unable to rescue the negative production effects of severe natural nutritional restriction on both the dam and fetuses.
RESUMO
The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high-fat diet (HFD) to reveal obesity-prone (OP) and obesity-resistant (OR) phenotypes. The OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium-fat diet. Rats were then maintained in energy balance for 8 wk before OVX. After OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h·d, 6 d·wk, 15 m·min. Energy intake, spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance pre-OVX, and at three time points post-OVX: before weight regain, during early regain, and after regain. Data are presented as mean ± SE. Exercise attenuated weight regain after OVX in OP only (OP-EX, 123 ± 10 g; OP-SED, 165 ± 12 g; OR-EX, 121 ± 6 g; OR-SED, 116 ± 6 g), which was primarily an attenuation of fat gain. The early post-OVX increase in energy intake explained much of the weight regain, and was similar across groups. Exercising improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to post-OVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA after ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction.
Assuntos
Densidade Óssea/fisiologia , Menopausa/fisiologia , Mitocôndrias Musculares/fisiologia , Obesidade/fisiopatologia , Consumo de Oxigênio/fisiologia , Condicionamento Físico Animal/fisiologia , Aumento de Peso/fisiologia , Animais , Composição Corporal/fisiologia , Metabolismo Energético , Feminino , Modelos Animais , Músculo Esquelético/fisiologia , Ovariectomia , Ratos WistarRESUMO
Liver X receptors (LXRs) are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRα and LXRß, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRα is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRα as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.
Assuntos
Colesterol/metabolismo , Epitélio/metabolismo , Lactação/genética , Receptores X do Fígado/genética , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Benzoatos/farmacologia , Benzilaminas/farmacologia , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Lactação/metabolismo , Lipogênese/genética , Receptores X do Fígado/metabolismo , Camundongos , RNA Mensageiro/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
Background: Evidence in humans is equivocal in regards to whether resting energy expenditure (REE) decreases to a greater extent than predicted for the loss of body mass with weight loss, and whether this disproportionate decrease in REE persists with weight-loss maintenance. Objectives: We aimed to1) determine if a lower-than-predicted REE is present in a sample of successful weight-loss maintainers (WLMs) and 2) determine if amount of weight loss or duration of weight-loss maintenance are correlated with a lower-than-predicted REE in WLMs. Design: Participants (18-65 y old) were recruited in 3 groups: WLMs (maintaining ≥13.6 kg weight loss for ≥1 y, n = 34), normal-weight controls [NCs, body mass index (BMI; in kg/m2) similar to current BMI of WLMs, n = 35], and controls with overweight/obesity (OCs, BMI similar to pre-weight-loss maximum BMI of WLMs, n = 33). REE was measured (REEm) with indirect calorimetry. Predicted REE (REEp) was determined via 1) a best-fit linear regression developed with the use of REEm, age, sex, fat-free mass, and fat mass from our control groups and 2) three standard predictive equations. Results: REEm in WLMs was accurately predicted by equations developed from NCs and OCs (±1%) and by 3 standard predictive equations (±3%). In WLMs, individual differences between REEm and REEp ranged from -257 to +163 kcal/d. A lower REEm compared with REEp was correlated with amount of weight lost (r = 0.36, P < 0.05) but was not correlated with duration of weight-loss maintenance (r = 0.04, P = 0.81). Conclusions: We found no consistent evidence of a significantly lower REE than predicted in a sample of long-term WLMs based on predictive equations developed from NCs and OCs as well as 3 standard predictive equations. Results suggest that sustained weight loss may not always result in a substantial, disproportionately low REE. This trial was registered at clinicaltrials.gov as NCT03422380.
Assuntos
Adaptação Fisiológica , Metabolismo Basal/fisiologia , Manutenção do Peso Corporal/fisiologia , Obesidade/metabolismo , Descanso/fisiologia , Redução de Peso/fisiologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Calorimetria Indireta , Estudos de Casos e Controles , Metabolismo Energético , Feminino , Humanos , Modelos Lineares , Masculino , Conceitos Matemáticos , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/terapia , Sobrepeso , Estudos Prospectivos , Termogênese , Fatores de Tempo , Adulto JovemRESUMO
Adipose tissue expansion progresses rapidly during postnatal life, influenced by both prenatal maternal factors and postnatal developmental cues. The ratio of omega-6 (n-6) relative to n-3 polyunsaturated fatty acids (PUFAs) is believed to regulate perinatal adipogenesis, but the cellular mechanisms and long-term effects are not well understood. We lowered the fetal and postnatal n-6/n-3 PUFA ratio exposure in wild-type offspring under standard maternal dietary fat amounts to test the effects of low n-6/n-3 ratios on offspring adipogenesis and adipogenic potential. Relative to wild-type pups receiving high perinatal n-6/n-3 ratios, subcutaneous adipose tissue in 14-day-old wild-type pups receiving low n-6/n-3 ratios had more adipocytes that were smaller in size; decreased Pparγ2, Fabp4, and Plin1; several lipid metabolism mRNAs; coincident hypermethylation of the PPARγ2 proximal promoter; and elevated circulating adiponectin. As adults, offspring that received low perinatal n-6/n-3 ratios were diet-induced obesity (DIO) resistant and had a lower positive energy balance and energy intake, greater lipid fuel preference and non-resting energy expenditure, one-half the body fat, and better glucose clearance. Together, the findings support a model in which low early-life n-6/n-3 ratios remodel adipose morphology to increase circulating adiponectin, resulting in a persistent adult phenotype with improved metabolic flexibility that prevents DIO.
Assuntos
Adipogenia , Glicemia/metabolismo , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Metabolismo dos Lipídeos , Obesidade/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adipócitos/citologia , Adiponectina/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células , Tamanho Celular , Metilação de DNA , Dieta Hiperlipídica , Gorduras na Dieta , Ingestão de Energia , Metabolismo Energético , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Camundongos , Obesidade/sangue , PPAR gama/metabolismo , Perilipina-1/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de RiscoRESUMO
Using a nonsteroidal anti-inflammatory drug (NSAID) before a single bout of mechanical loading can reduce bone formation response. It is unknown whether this translates to an attenuation of bone strength and structural adaptations to exercise training. PURPOSE: This study aimed to determine whether nonsteroidal anti-inflammatory drug use before exercise prevents increases in bone structure and strength in response to weight-bearing exercise. METHODS: Adult female Wistar rats (n = 43) were randomized to ibuprofen (IBU) or vehicle (VEH) and exercise (EX) or sedentary (SED) groups in a 2 × 2 (drug and activity) ANCOVA design with body weight as the covariate, and data are reported as mean ± SE. IBU drops (30 mg·kg BW) or VEH (volume equivalent) were administered orally 1 h before the bout of exercise. Treadmill running occurred 5 d·wk for 60 min·d at 20 m·min with a 5° incline for 12 wk. Micro-CT, mechanical testing, and finite element modeling were used to quantify bone characteristics. RESULTS: Drug-activity interactions were not significant. Exercise increased tibia cortical cross-sectional area (EX = 5.67 ± 0.10, SED = 5.37 ± 0.10 mm, P < 0.01) and structural estimates of bone strength (Imax: EX = 5.16 ± 0.18, SED = 4.70 ± 0.18 mm, P < 0.01; SecModPolar: EX = 4.01 ± 0.11, SED = 3.74 ± 0.10 mm, P < 0.01). EX had increased failure load (EX = 243 ± 9, SED = 202 ± 7 N, P < 0.05) and decreased distortion in response to a 200-N load (von Mises stress at tibia-fibula junction: EX = 48.2 ± 1.3, SED = 51.7 ± 1.2 MPa, P = 0.01). There was no effect of ibuprofen on any measurement tested. Femur results revealed similar patterns. CONCLUSION: Ibuprofen before exercise did not prevent the skeletal benefits of exercise in female rats. However, exercise that engenders higher bone strains may be required to detect an effect of ibuprofen.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Osso Cortical/efeitos dos fármacos , Ibuprofeno/farmacologia , Osteogênese/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Animais , Osso Cortical/anatomia & histologia , Osso Cortical/fisiologia , Feminino , Humanos , Osteogênese/fisiologia , Distribuição Aleatória , Ratos Wistar , Treinamento ResistidoRESUMO
UNLABELLED: Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with a high-fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild-type or fructokinase knockout mice were fed a low-fat (11%), high-fat (36%), or high-fat (36%) and high-sucrose (30%) diet for 15 weeks. Both wild-type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence of hepatic inflammation on a high-fat diet compared to a low-fat diet. In contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis with low-grade inflammation and fibrosis, as noted by increased CD68, tumor necrosis factor alpha, monocyte chemoattractant protein-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. CONCLUSION: An additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high-fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis.