RESUMO
OBJECTIVES: To investigate the effects of chronic stress on bladder morphology and the impact of food preference (standard or comfort foods) on the bladder of stressed rats. METHODS: In total, 32 Wistar male rats (3 months old) were divided into four groups: control (C), stressed (S), control + comfort food (C + CF), and stressed + comfort food (S + CF). Groups C and C + CF were maintained under normal conditions, while groups S and S + CF were subjected to chronic stress by the restraint method. Groups C and S received standard rat chow, while groups C + CF and S + CF received comfort food (Froot Loops®) and standard chow. The stress stimuli were induced daily for 2 h over 8 weeks. After 8 weeks, all animals were killed, and the bladders were removed and used for histomorphometric analysis. RESULTS: Body mass was similar among the groups. Stress did not promote differences regarding food intake, but animals receiving comfort food showed higher calories intake (in kcal/Kg) than animals receiving only standard chow. The C + CF and S + CF groups preferred comfort food over the standard chow; this preference was higher in the S + CF than in the C + CF group. The surface density of smooth muscle was reduced in stressed animals, while connective tissue and elastic system fiber content were increased in stressed groups. Further, epithelial height was increased in rats submitted to chronic stress. The surface density of elastic system fibers was decreased by the consumption of comfort food. CONCLUSIONS: Chronic stress induces morphological modifications on the bladder wall and epithelium. These modifications may be related to lower urinary tract symptoms. Additionally, chronic stress caused a higher preference for comfort food intake which did not ameliorate or aggravate the stress-induced bladder alterations.
Assuntos
Ingestão de Alimentos , Bexiga Urinária , Ratos , Masculino , Animais , Ingestão de Alimentos/fisiologia , Ratos Wistar , Estresse Psicológico , Ingestão de EnergiaRESUMO
Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS - 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) - via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.
Assuntos
Antioxidantes , Quercetina , Ratos , Feminino , Animais , Humanos , Ratos Wistar , Quercetina/farmacologia , Antioxidantes/farmacologia , Oxirredução , Estrogênios , Tecido Adiposo Branco , Homeostase , OvariectomiaRESUMO
Purpose: To investigate the effects of chronic stress, associated or not with comfort food, on the morphology of the penis. Materials & methods: Thirty-two adult Wistar rats were divided into four experimental groups: Control group (C), receiving standard rat chow, and under normal conditions; Stressed group (S), receiving standard chow, and submitted to stressful situations; Control + comfort food group (C + CF), receiving standard chow and comfort food, and under normal conditions; and Stressed + comfort food group (S + CF), receiving standard chow and comfort food, and submitted to stressful situations. At 10 weeks of age, food supply and stress were initiated. All groups had ad libitum access to standard chow and water, and groups receiving comfort food also had access to Froot Loops®. Chronic stress was induced by restriction, animals were contained daily in polypropylene tubes for 2 h, for eight weeks. After eight weeks all animals were killed; penises were removed for histomorphometric analysis. Results: Body mass was similar among the groups. Food intake in S + CF group was lower than in other groups. Concerning food preference, groups C + CF and S + CF preferred comfort food over the standard chow, with this preference being higher in S + CF than in C + CF. The area of the corpora cavernosa without tunica albuginea was lower in group S + CF than in group C. Most interestingly, the surface density of connective tissue in the corpora cavernosa was higher in groups S and S + CF compared to group C. In contrast, smooth muscle surface density was markedly lower in S + CF compared to groups C and C + CF, while group S also had reduced smooth muscle in comparison to group C. Conclusion: Chronic stress caused a morphological alteration on penile histomorphometry. Also, stress increased the preference for comfort foods which caused more deleterious effects in some parameters.
RESUMO
Small renal masses have been diagnosed increasingly in recent decades, allowing surgical treatment by partial nephrectomy. This treatment option is associated with better renal function preservation, in comparison with radical nephrectomy. However, for obtaining a bloodless field during surgery, occlusion of renal artery and veins is often required, which results in transitory ischemia. The renal ischemia-reperfusion injury is associated with increased reactive oxygen species production leading to renal tissue damage. Thus, the use of antioxidants has been advocated in the partial nephrectomy perioperative period. Several antioxidants were investigated in regard to renal ischemia-reperfusion injury. The present manuscript aims to present the literature on the most commonly studied antioxidants used during partial nephrectomy. The results of experimental and clinical studies using antioxidants during partial nephrectomy are reported. Further, alimentary sources of some antioxidants are presented, stimulating future studies focusing on perioperative antioxidant-rich diets.
Assuntos
Antioxidantes/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Traumatismo por Reperfusão/tratamento farmacológico , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/cirurgia , Neoplasias Renais/fisiopatologia , Nefrectomia , Período Perioperatório , Artéria Renal/efeitos dos fármacos , Artéria Renal/patologia , Artéria Renal/cirurgia , Traumatismo por Reperfusão/fisiopatologiaRESUMO
High-fat diets affect male reproduction and sexual function. Therefore, we evaluated the effects of prolonged resveratrol administration on the metabolic, sperm, and testicular parameters of rats fed a cafeteria diet. Male Wistar rats were divided at weaning into control (C, n = 20) and cafeteria (CAF, n = 16) groups. At 3 months, half of them were given daily supplementations of resveratrol (C-R, n = 10; CAF-R, n = 8) at a dosage of 30 mg kg-1 body mass for 2 months. Animals were killed at 5 months of age, and blood, spermatozoa, and testes were collected for further analysis. Data were analyzed by one-way ANOVA, and P < 0.05 was considered statistically significant. The CAF diet promoted hyperglycemia (P < 0.0001), and treatment with resveratrol reversed this condition (P < 0.0001). The CAF diet reduced sperm viability and motility, while resveratrol improved these parameters (P < 0.05). Regarding testicular morphology, the height of the seminiferous epithelium was reduced in the CAF group compared with that of the C group (P = 0.0007). Spermatogenic cell proliferation was also reduced in the CAF group compared with that of the C group. However, the CAF-R showed an increase in cell proliferation rate compared with that of the untreated CAF group (P = 0.0024). Although it did not modify body mass, the consumption of a CAF diet promoted hyperglycemia, adverse testicular morphology remodeling, and abnormal sperm, which were attenuated by treatment with resveratrol, thus suggesting a protective effect of this antioxidant on spermatogenesis.
Assuntos
Antioxidantes/farmacologia , Hiperglicemia/tratamento farmacológico , Resveratrol/farmacologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Glicemia , Proliferação de Células/efeitos dos fármacos , Dieta Hiperlipídica , Hiperglicemia/metabolismo , Lipídeos/sangue , Masculino , Ratos , Ratos Wistar , Resveratrol/uso terapêutico , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/metabolismoRESUMO
Vitamin D deficiency is common in pregnant women and infants. The present study aimed to investigate the effects of vitamin D restricted diet on the Wistar rats offspring penis morphology. Mother rats received either standard diet (SC) or vitamin D restricted (VitD) diet. At birth, offspring were divided into SC/SC (from SC mothers, fed with SC diet) and VitD/VitD (from VitD mothers, fed with VitD diet). After euthanasia the penises were processed for histomorphometric analysis. The VitD/VitD offspring displayed metabolic changes and reduction in the cross-sectional area of the penis, corpus cavernosum, tunica albuginea, and increased area of the corpus spongiosum. The connective tissue, smooth muscle, and cell proliferation percentages were greater in the corpus cavernosum and corpus spongiosum in the VitD/VitD offspring. The percentages of sinusoidal spaces and elastic fibers in the corpus cavernosum decreased. The elastic fibers in the tunica albuginea of the corpus spongiosum in the VitD/VitD offspring were reduced. Vitamin D restriction during perinatal and postnatal periods induced metabolic and structural changes and represented important risk factors for erectile dysfunction in the penis of the adult offspring. These findings suggest that vitamin D is an important micronutrient in maintaining the cytoarchitecture of the penis.
Assuntos
Pênis , Complicações na Gravidez , Deficiência de Vitamina D , Vitamina D , Animais , Feminino , Masculino , Pênis/citologia , Pênis/efeitos dos fármacos , Pênis/crescimento & desenvolvimento , Gravidez , Ratos , Ratos Wistar , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/farmacologiaRESUMO
Here, we evaluated the effects of a high-fat diet during the prenatal and/or postnatal period on the metabolic parameters and testes of 4-month-old Wistar rats. The experimental groups, composed of male Wistar rats, were: C/C (n=8), HF/HF (n=8) (pups with the same diet as their dams, after weaning), C/HF (n=8), and HF/C (n=9) (pups with a different diet after weaning, from that of their dams). The biometric parameters, blood glucose levels, serum levels, the gonadosomatic index, sperm parameters, testes, and genital fat deposits were evaluated. The HDL-c serum levels were significantly lower in the C/HF group (P=0.0100), whereas animals in the HF/C group presented hypertriglyceridemia (P=0.0005). The sperm concentration was lower in the HF/HF group than in the HF/C group (P=0.0072), and sperm viability was lower in all groups receiving a high-fat diet (P<0.0001). The tubular compartment was the smallest in the HF/HF group (P<0.0001). The diameter of the seminiferous tubule was the widest in the HF/C group (P<0.0001). The height of the seminiferous epithelium in all groups was lower than that in the C/C group (PP<0.0001). Testosterone and steroidogenic acute regulatory protein (STAR) expression levels were lower in the C/HF group (P=0.0218 and P=0.0215, respectively). The HF diet, regardless of the administration period, induced a limited number of metabolic changes, and modifications in the histoarchitecture of the testes and sperm parameters. These data suggest that a HF diet may cause disturbances in spermatogenesis and fertility impairment in adulthood.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Fenômenos Fisiológicos da Nutrição Pré-Natal , Espermatogênese , Testículo/patologia , Animais , Feminino , Fertilidade , Masculino , Gravidez , Ratos , Ratos WistarRESUMO
ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.
Assuntos
Animais , Masculino , Ratos , Próstata/patologia , Próstata/ultraestrutura , Testosterona/sangue , Orquiectomia , Terapia de Reposição Hormonal , Androgênios/deficiência , Próstata/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. MATERIALS AND METHODS: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. RESULTS: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29µm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. CONCLUSION: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations.
Assuntos
Androgênios/deficiência , Terapia de Reposição Hormonal , Orquiectomia , Próstata/patologia , Próstata/ultraestrutura , Testosterona/sangue , Animais , Masculino , Próstata/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To evaluate the effects of different high-fat diets on body mass, carbohydrate metabolism and testicular morphology in rats seven months old. MATERIALS AND METHODS: Male Wistar rats were divided into four groups: SC (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood samples, testes and genital fat deposits were collected for analysis. Data were analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as statistically significant. RESULTS: Different high-fat diets promoted an increase in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC group (p=0.0010). CONCLUSIONS: The high fat diet administration, independent of the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard) alters the carbohydrate metabolism and the testicular morphology with reductions of seminiferous epithelium height, seminiferous tubule diameter and cell proliferation which could be related to a disturbance of spermatogenesis.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/metabolismo , Testículo/anatomia & histologia , Testículo/metabolismo , Animais , Colesterol/sangue , Ácidos Graxos/efeitos adversos , Ácidos Graxos/metabolismo , Imuno-Histoquímica , Leptina/sangue , Masculino , Tamanho do Órgão , Sobrepeso/metabolismo , Ratos Wistar , Valores de Referência , Espermatogênese , Testosterona/sangue , Fatores de Tempo , Triglicerídeos/sangueRESUMO
To evaluate the effects of different high-fat diets on body mass, carbohydrate metabolism and testicular morphology in rats seven months old.
Male Wistar rats were divided into four groups: SC (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood samples, testes and genital fat deposits were collected for analysis. Data were analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as statistically significant.
Different high-fat diets promoted an increase in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC group (p=0.0010).
The high fat diet administration, independent of the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard) alters the carbohydrate metabolism and the testicular morphology with reductions of seminiferous epithelium height, seminiferous tubule diameter and cell proliferation which could be related to a disturbance of spermatogenesis.
Assuntos
Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/metabolismo , Testículo/anatomia & histologia , Testículo/metabolismo , Colesterol/sangue , Ácidos Graxos/efeitos adversos , Ácidos Graxos/metabolismo , Imuno-Histoquímica , Leptina/sangue , Tamanho do Órgão , Sobrepeso/metabolismo , Ratos Wistar , Valores de Referência , Espermatogênese , Fatores de Tempo , Testosterona/sangue , Triglicerídeos/sangueRESUMO
OBJECTIVE: We sought to evaluate the effects of telmisartan, sitagliptin, or their combination on pancreatic ultrastructural alterations in high-fat-fed C57BL/6 mice. METHODS: Three-month-old C57BL/6 mice were fed with standard chow (SC, 10% lipids) or high-fat diet (HF, 60% lipids) during 10 weeks to induce obesity and its comorbidities. After this period, treatment began (lasted 6 weeks), and the HF group was divided into 4 subgroups: untreated HF, HF plus telmisartan (5 mg/kg per day), HF plus sitagliptin (1.1 g/kg per day), and HF plus telmisartan plus sitagliptin. Drugs were mixed with diet. Biochemical analyses, radioimmunoassay, immunofluorescence, stereology, and transmission electron microscopy were performed to assess pancreatic remodeling. RESULTS: Overweight, hyperinsulinemia, hyperglycemia, and dyslipidemia were found in the HF group, but these outcomes were controlled by the different treatments. Untreated HF animals also showed alterations concerning distribution of α/ß cell followed by large and numerous lipid droplets within pancreas. Telmisartan and sitagliptin as monotherapy alleviated these findings, and a complete reversal of pancreatic steatosis was observed after treating with the combination of the 2 drugs. CONCLUSIONS: AT1 receptor blockade, partial peroxisome proliferator-activated receptor gamma activation, and extended incretin action emerge as feasible strategies to control pancreatic steatosis and avoid progression of pancreatic diseases due to lipotoxicity.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Obesidade/tratamento farmacológico , Obesidade/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/ultraestrutura , Pirazinas/administração & dosagem , Triazóis/administração & dosagem , Animais , Glicemia/metabolismo , Gorduras na Dieta/administração & dosagem , Quimioterapia Combinada , Insulina/sangue , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/ultraestrutura , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Pâncreas/metabolismo , Pâncreas Exócrino/efeitos dos fármacos , Pâncreas Exócrino/metabolismo , Pâncreas Exócrino/ultraestrutura , Fosfato de Sitagliptina , TelmisartanRESUMO
OBJECTIVE: This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes nonalcoholic fatty liver disease in adult C57BL/6 mice offspring. STUDY DESIGN: Male pups were divided into 5 groups: (1) SC, from standard chow-fed dams; (2) G, from high-fat chow (HF)-fed dams during the gestation (G) period; (3) L, from HF-fed dams during the lactation (L) period; (4) GL, from HF-fed dams during the gestation and lactation (GL) periods; and (5) GL/HF, from HF-fed dams during GL, maintaining an HF diet from postweaning to adulthood. We analyzed body mass, plasma blood, and liver structure. RESULTS: The G offspring showed insulin resistance and lower glucose transporter-2 expression. Hepatic steatosis was present in the G, L, GL, and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c expression was higher in G, GL, and GL/HF offspring. CONCLUSION: Programming by HF chow predisposes hepatic adverse remodeling in the liver of adult offspring.
Assuntos
Gorduras na Dieta/metabolismo , Fígado Gorduroso/etiologia , Fígado/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Análise de Variância , Animais , Glicemia , Western Blotting , Peso Corporal , Suscetibilidade a Doenças/metabolismo , Ensaio de Imunoadsorção Enzimática , Fígado Gorduroso/metabolismo , Feminino , Teste de Tolerância a Glucose , Insulina/sangue , Resistência à Insulina , Masculino , Camundongos , Gravidez , Radioimunoensaio , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The aim of the present study was to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, and pancreatic and hepatic remodelling in C57BL/6 mice fed on a very HF (high-fat) diet. Male C57BL/6 mice were fed on an HF (60% lipids) diet or SC (standard chow; 10% lipids) diet for 10 weeks, after which time the following drug treatments began: HF-T (HF diet treated with telmisartan; 5.2 mg x kg-1 of body weight x day-1), HF-S (HF diet treated with sitagliptin; 1.08 g x kg-1 of body weight.day-1), HF-M (HF diet treated with metformin; 310.0 mg x kg-1 of body weight x day-1), HF-TM (HF diet treated with telmisartan+metformin), HF-TS (HF diet treated with telmisartan+sitagliptin) and HF-SM (HF diet treated with sitagliptin+metformin). Treated groups also had free access to the HF diet, and treatments lasted for 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blot analysis and electron microscopy were used. The HF diet yielded an overweight phenotype, an increase in oral glucose intolerance, hyperinsulinaemia, hypertrophied islets and adipocytes, stage 2 steatosis (>33%), and reduced liver PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and GLUT-2 (glucose transporter-2) levels, concomitant with enhanced SREBP-1 (sterol-regulatory-element-binding protein-1) expression (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, a reversal of insulin resistance, islet and adipocyte hypertrophy, and alleviated hepatic steatosis. Only the HF-T and HF-TS groups had body weights similar to the SC group at the end of the experiment, and the latter treatment reversed hepatic steatosis. Increased PPAR-alpha immunostaining in parallel with higher GLUT-2 and reduced SREBP-1 expression may explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-alpha (tumour necrosis factor-alpha) levels (P<0.0001) in the drug-treated groups. In conclusion, all of the drug treatments were effective in controlling the metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-gamma agonism and PPAR-alpha activation in the liver with extended incretin action.