Adult Obese Rats Research Articles

Effect of orlistat versus lipo-6 black on the testis of adult obese albino rats: histological and histomorphometric study

Background Obesity is a health problem with increasing incidence. Excess fat is the most common factor that contributes to its pathogenesis. Aim To evaluate the effect of obesity on the testis of male rats and compare the possible ameliorative effect of orlistat versus lipo-6. Materials and methods Fifty-six adult male rats were used. The control group ‘eight rats’ received a standard diet (SD) with no treatment for 90 days. The experimental group ‘48 rats’ received high-fat diet (HFD) for 60 days for obesity induction. Obese rats were subdivided into three groups (each group a and b). IIa received SD and IIb received HFD. IIIa received SD+orlistat and IIIb received HFD+orlistat. IVa received SD+lipo-6. IVb received HFD+lipo 6. The drugs were used for 30 days. Testicular specimens were subjected to histological, histomorphometrical, and immunohistochemical examinations. Data on obesity index, testis weight, abdominal circumference sperm percentage, and histomorphometry were analyzed statistically. Results Subgroups IIIa and IVa showed restoration of the structural integrity of the seminiferous tubules with the normal distribution of collagen fibers. Sections of subgroup IIIa showed negative caspase-3 immunostaining near the control group. Lee obesity index and percentage of abnormal sperm were close to control. Conclusion Orlistat and lipo-6 with diet adjustment reduced the severity of testicular damage induced by obesity.

Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is already impacted during adolescence in a genetic rat model for obesity and type 2 diabetes. Visual discrimination learning throughout adolescence and the level of motivation during early adulthood were investigated in Zucker Diabetic Fatty (ZDF) obese and ZDF lean rats using operant touchscreens. Blood glucose, insulin, and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues, and the prefrontal cortex. Prior to the experiments with the genetic ZDF research model, all experimental assays were performed in two groups of outbred Long Evans rats to investigate the effect of different feeding circumstances. Adolescent ZDF obese rats outperformed ZDF lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in early adult ZDF obese rats. Histological analyses in early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent ZDF obese rats even display enhanced cognition despite their early diabetic profile.

Effect of phenotype on thyroidal parameters and metabolic sequelae in Wistar fatty rats

To determine the effects of phenotype on parameters of peripheral thyroid hormone and actions, groups of adult male lean (LN) and obese (OB) Wistar Fatty Rats were fed a nutritionally adequate semisynthetic diet containing 54% carbohydrate, 16% mixed fats, 20% protein plus essential vitamins, minerals, and cellulose fiber for 8 weeks. Measures of weight gain (WG), feed efficiency ratio (FER), Resting (RMR) and norepinephrine (NE) stimulated VO2, serum triiodothyronine (T3), and in vitro T4-5’ deiodinase (5’DI) activity in liver (LVR), kidney (KID), gastrocnemius muscle (GNM) and interscapular brown adipose tissue (IBAT) were determined at baseline and after dithiothreitol (DTT) stimulation to optimize in vitro deiodination activity. The WG and FER of OB >> LN phenotype and FER increased over time in both phenotypes, with the greatest increase in the OB phenotype. The RMR of LN > OB, and NE-stimulation (200 µg/kg BW, sc) increased VO2 by 180% in LN but only ~30% in OB phenotype. Serum T3 of LN >> OB. Baseline 5’DI of OB > LN in LIV and KID and were of similar magnitude in both phenotypes in GNM and IBAT. After DTT stimulation, LIV increased ~200% in LN, ~30% in OB; In LN rats, KID +DTT increased ~200%, but only modest increases in OB phenotype, while in LN GNM, DTT resulted in 264% increase vs. +70% in OB rats. In IBAT, DTT resulted in ~ 30-fold increase in 5’DI in LN, and a 16-fold increase in 5’DI in the OB phenotype. These results indicate that parameters of thyroidal actions including circulating plasma levels of T3 and maximum capacity to generate T3 in peripheral tissues via 5’DI, although increased in the OB phenotype, were associated with decreases in RMR and NE-stimulated VO2. These observations occurred in association with an improved efficiency of FER and weight gain and dysregulation of intracellular T3 actions including parameters of T3 receptor affinity kinetics are likely to be among key contributors to the epigenetic expression of the OB+NIDDM phenotype in this strain and are consistent with a reduced affinity of T3- mediated cellular components of intermediary metabolism.

Kefir milk consumption decreases sperm alterations due to the high‐fat diet in adult male rats

Over the past decades, an increase of male infertility through the decrease of sperm count has been noted. It has been suggested that environmental factors and lifestyle could a negative impact over sperm quality. Among these factors, the consumption of foods high in fat, which leads to overweight and obesity, can negatively influence fertility. The present study was designed to highlight the protective effect of Kefir, natural probiotic, against the decline in sperm quality related to fat high diet. Thirty adult rats were divided into four groups: Control (1ml/100g of body weight (bw) of semi-shimmed cow milk), KM (1ml/100g bw of Kefir milk), HFD (1ml/100g bw of semi-shimmed cow milk + high-fat diet) and KM/HFD (1ml/100g bw Kefir milk + high-fat diet). After 60days of treatment, sperm quality, biochemical assays of lipids profil, blood cell count and histological examination in testis were assessed. The results described an improved of sperm density (64.28 106 ml vs 54.14 106 ml), viability (70.50% vs 55.33%), mobility (65.40% vs 63.60%) and morphological abnormalities (52% vs 25%) in the KM/HFD group compared to HFD group. In the same group, the lipid profil (Triglycerides (128.39mg/dl vs 102.85mg/dl), C-LDL (13.65mg/dl vs 15.32mg/dl) and C-HDL (23.21mg/dl vs 19.15mg/dl)) was corrected compared to HFD group. The histological observation of testis revealed a normal spermatogenesis compared to seminiferous tubules of HFD group, which showed a serious disruption and damage of testicular epithelium exerted by the high-fat diet. These findings corroborated the previous beneficial effect of Kefir and brought new insights into its beneficial effect against deteriorated spermatogenesis in obese adult rats.

Mitochondrial Adaptations of Obese Adult Rat Visceral Adipocytes which Differ in Nutritional Status during Childhood

Mitochondria are highly dynamic organelles that can adapt to different environmental stimuli. This study aims to analyze differences in the function and biogenesis of mitochondria and anaerobic glycolysis activity between obese adult rats that were undernourished in childhood (LCD28) and those which were normal (SD28) or already fat (HFD28). Sprague-dawley rats were assigned groups and given diet treatments from December 2017 until August 2018 in the Laboratory Animal Management Unit, Faculty of Veterinary Medicine, Bogor Agricultural Institute. To observe mitochondrial function and biogenesis, MnSOD activity and PGC1α levels were analyzed using ELISA. To investigate the existence of anaerobic glycolysis, LDH activity was analyzed using a spectrophotometry method. The results showed that MnSOD activity and PGC1α levels of LCD28 increased compared to the other groups, signifying higher mitochondrial function and biogenesis. Meanwhile, no significant difference in LDH activity was found, signifying similar levels of anaerobic glycolysis.

Sex-specific effects of metformin and liraglutide on renal pathology and expression of connexin 45 and pannexin 1 following long-term high-fat high-sugar diet

The comparative effects of the two commonly used antidiabetic drugs metformin and liraglutide on renal pathology and expression of connexin 45 (Cx45) and pannexin 1 (Panx1) in adult obese rats fed high-fat high-sugar diet (HFHSD) were studied. Considering recent data on the profound influence of sex on metformin and liraglutide effects, we compared the effects of both drugs between male and female animals. 44-week-old Sprague-Dawley rats were separated into 4 groups that were fed: standard diet, HFHSD, HFHSD treated with metformin (s.c., 50 mg/kg/day) and HFHSD treated with liraglutide (s.c., 0.3 mg/kg/day). Treatment with metformin or liraglutide lasted for 14 weeks. Histology and immunohistochemistry were performed to quantify renal pathological changes and Cx45 and Panx1 expression. HFHSD caused thickening of the Bowman’s capsule (BC). Both metformin and liraglutide failed to ameliorate the BC thickening; metformin even worsened it. Effects on the tubulointerstitial fibrosis score, BC thickness and Cx45 and Panx1 expression were sex-dependent. We found a 50% increase in mitochondria in proximal tubules of metformin- and liraglutide-treated HFHSD-fed rats, but these effects were not dependent on the sex. This is a first study showing that the effects of metformin and liraglutide on kidney pathology in rats fed HFHSD are mostly sex-dependent and that these effects are not necessarily beneficial. Both drugs changed the Cx45 and Panx 1 expression; hence their effects could be related to amelioration of disruptions in intercellular communication.

Responses of Visfatin and Resistin Concentration to Different Aerobic Training Intensities Protocols

Background: Visfatin and resistin are adipokines involved in metabolic regulation and physiological processes. Objectives: This study aimed to investigate the effects of eight weeks of aerobic training with different intensities on serum levels of resistin and visfatin in obese male rats. Methods: 24 adult obese rats (weight: 250 to 300 gr, BMI > 30 g/cm2) divided into three groups: aerobic training with 28 m/min (moderate intensity), aerobic training with 34 m/min (high intensity) and, control group. All training groups did exercise training for 8 weeks (5 sessions/per-week for 60 minutes per session). 48 hours after the training period, the level of serum visfatin and resistin levels was measured. Results: Unlike the levels of resistin concentration (P = 0.001) in different groups, there was no significant difference between visfatin levels in all three groups. Resistin concentration was not significantly changed in the moderate-intensity group compared to the control group, (185.10 ± 12.85 vs. 202.76 ± 17.39) (P = 0.05). There was a significant difference between the high intensity and control groups (P = 0.001). There was no significant difference in visfatin concentration in MI and HI groups compared to the control group (P > 0.05). Conclusions: There is a significant difference in the levels of resistin concentration in different groups. There was no significant difference between visfatin levels in all three groups. Therefore, it seems that aerobic training with high intensity has a better effect on the prevention of obesity and cardiovascular disease.

Impaired metabolic and hepatic functions following subcutaneous lipectomy in adult obese rats.

What is the central question of this study? What is the impact and drawbacks of subcutaneous lipectomy on body metabolism? What is the main finding and its importance? Subcutaneous lipectomy resulted in deterioration of hepatic functions, atherosclerotic lipid profile and disturbed redox state. While the results support lipectomy as an effective treatment for obesity, lipectomy induces unfavourable changes in health. The number of obese older adults is on the rise, but data about proper treatment of obesity in the elderly is controversial. The present study was designed to investigate the effectiveness and consequences of partial subcutaneous lipectomy, as a rapid medical intervention against increased accumulation of body fat, in adult obese rats. The study was conducted on adult (9-12months) female rats, in which obesity was induced by bilateral surgical ovariectomy. They were randomized into two main groups: short term (5weeks) and long term (10weeks). Both groups were subdivided into control, ovariectomized (OVX) and ovariectomized lipectomized groups. Body weight (BW) was measured and body mass index (BMI) calculated. Fasting blood glucose, lipid profile and plasma levels of total proteins, albumin, liver enzymes, malondialdehyde (MDA), leptin and adiponectin were determined. The content of both blood and hepatic tissue of reduced glutathione was estimated. In addition, histological study of the liver, aorta and peri-renal fat was performed. Compared to controls, OVX rats showed significant increase in BW, BMI and plasma levels of liver enzymes, MDA and leptin. Histological study revealed vacuolated ballooned hepatocytes and enlarged irregular visceral adipocytes with atherosclerotic changes in the wall of aorta. Following subcutaneous lipectomy, rats exhibited significant fasting hyperglycaemia, dyslipidaemia, lowered plasma albumin and disturbed redox state with aggravation of the histological changes. The findings indicate that although subcutaneous lipectomy appears to be effective in combating obesity in older females, it has unfavourable effects on both metabolic and hepatic functions.

Altered endocrine, cytokine signaling and oxidative stress: A plausible reason for differential changes in testicular cells in diet-induced and genetically-inherited – obesity in adult rats

Obesity is emerging as a potential risk factor for male infertility. It is a multifactorial disorder with primarily genetic and/or environmental factors. Our earlier studies have shown differential effects of genetically inherited-and high fat diet induced-obesity on hormones, fertility and spermatogenesis in adult male rats. In the present study, we assessed the effect of high fat diet induced – and genetically inherited – obesity on the underlying molecular mechanisms affecting spermatogenesis. The expression of hormone receptors, cytokines and markers of oxidative stress as well as cell cycle mediators were affected in both the obese groups, however, the changes were different in the two groups. This could be due to difference in fat distribution between the two types of obese groups. Altered expression of hormone receptors, cytokines, cell cycle mediators and differential effects on oxidative stress could be the plausible reason for differential changes in germ cell population in both the groups.

Monosodium l-glutamate-obesity onset is associated with disruption of central control of the hypothalamic-pituitary-adrenal axis and autonomic nervous system.

The hypothalamic-pituitary-adrenal axis (HPA) exerts important catabolic peripheral effects and influences autonomic nervous system (ANS)-mediated processes. Impaired negative-feedback control or reduced HPA axis sensitivity and altered ANS activity appear to be associated with the development and maintenance of obesity. In the present study, we examined the hypothesis that the central HPA axis is dysregulated favouring ANS disbalance in monosodium l-glutamate (MSG)-induced rat obesity. Glucose homeostasis, corticosterone, leptin and ANS electrical activity were evaluated. Adult MSG-induced obese rats exhibited fasting hyperinsulinaemia, insulin resistance, glucose intolerance, hypercorticosteronaemia, hyperleptinaemia and altered ANS activity. A decrease in food intake was observed during corticotrophin-releasing hormone (CRH) treatment in both control and MSG-treated rats. By contrast, food intake was significantly elevated in control rats treated with dexamethasone (DEXA), whereas no alterations were observed following DEXA treatment in MSG-induced obese rats. After DEXA injection, an increase in fasting insulin and glucose levels, associated with insulin resistance, was seen in both groups. As expected, there was a decrease of parasympathetic activity and an increase of sympathetic nervous activity in CRH-treated control animals and the opposite effect was seen after DEXA treatment. By contrast, there was no effect on ANS activity in MSG-rats treated with CRH or DEXA. In conclusion, impairment of the HPA axis can lead to disbalance of ANS activity in MSG-treated rats, contributing to the establishment and maintenance of obesity.

Role of irisin administration in modulating testicular function in adult obese albino rats

AbstractBackground: Irisin, exercise-induced myokine, is known to improve obesity-induced metabolic disturbances by enhanc-ing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promoted cell proliferation and protected cells from apoptosis. However, the effects of irisin on testicular function in obese rats is still to be investi-gated.Aim of the Study: This study was designed to explore the probable effects of irisin treatment on modulating the adverse effects of obesity on testicular functions with a trial to clarify some of the possible underlying mechanisms.Material and Methods: Thirty adult male wistar albino rats (200±30g) were divided equally into 3 groups, group (I): Saline-vehicle treated normal fed group, group (II): Saline-vehicle treated rats were fed a High Fat Diet (HFD) for 10 weeks. Group (III): Irisin treated HFD-fed rats for 10 weeks and irisin was injected subcutaneously (150ml daily for 4 weeks). Rats were weighed and serum levels of glucose, insulin, lipid profile, FSH, LH, estradiol & testosterone levels, epididymal sperm count and motility, testicular Malondiald-hyde (MDA) level, Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX) activities, testicular and epidydimal fat weights were estimated. Testicular his-topathological study was done as well.Results: There was a significant increase in the Body Mass Index (BMI) together with deterioration of metabolic, gonadal functions and testicular oxidant/antio-oxidant system in group (II), while exogenous irisin administration in group (III) resulted in: Significant decrease in BMI, insulin resistance with improvement in lipid profile, significant increase in serum FSH, LH & testosterone, sperm count and motility in male rats. Together with marked improvement in the testicular histoarchitecture. Additionally, there was a significant increase in testicular SOD, CAT & GPX activities. However, it signif-icantly decreased testicular MDA level.Conclusions: It could be suggested that irisin has a po-tential positive role against obesity-induced testicular dys-function, which may be due to its role in maintenance of glucose & insulin homeostasis, its antioxidant properties and/ or maintenance of gonadal hormonal function via indirect and/or direct effects on the gonads.

Role of Irisin Administration in Modulating Testicular Function in Adult Obese Albino Rats

AbstractBackground: Irisin, exercise-induced myokine, is known to improve obesity-induced metabolic disturbances by enhanc-ing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promoted cell proliferation and protected cells from apoptosis. However, the effects of irisin on testicular function in obese rats is still to be investi-gated.Aim of the Study: This study was designed to explore the probable effects of irisin treatment on modulating the adverse effects of obesity on testicular functions with a trial to clarify some of the possible underlying mechanisms.Material and Methods: Thirty adult male wistar albino rats (200±30g) were divided equally into 3 groups, group (I): Saline-vehicle treated normal fed group, group (II): Saline-vehicle treated rats were fed a High Fat Diet (HFD) for 10 weeks. Group (III): Irisin treated HFD-fed rats for 10 weeks and irisin was injected subcutaneously (150ml daily for 4 weeks). Rats were weighed and serum levels of glucose, insulin, lipid profile, FSH, LH, estradiol & testosterone levels, epididymal sperm count and motility, testicular Malondiald-hyde (MDA) level, Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX) activities, testicular and epidydimal fat weights were estimated. Testicular his-topathological study was done as well.Results: There was a significant increase in the Body Mass Index (BMI) together with deterioration of metabolic, gonadal functions and testicular oxidant/antio-oxidant system in group (II), while exogenous irisin administration in group (III) resulted in: Significant decrease in BMI, insulin resistance with improvement in lipid profile, significant increase in serum FSH, LH & testosterone, sperm count and motility in male rats. Together with marked improvement in the testicular histoarchitecture. Additionally, there was a significant increase in testicular SOD, CAT & GPX activities. However, it signif-icantly decreased testicular MDA level.Conclusions: It could be suggested that irisin has a po-tential positive role against obesity-induced testicular dys-function, which may be due to its role in maintenance of glucose & insulin homeostasis, its antioxidant properties and/ or maintenance of gonadal hormonal function via indirect and/or direct effects on the gonads.

A Study on the Immunological Changes in Adult Male Obese Rats and the Possible Immune Modulator Effect of Conjugated Linoleic Acid Supplementation

AbstractBackground: Conjugated Linoleic Acid [CLA] is suggested as a novel drug to improve obesity.Objectives: The aim of this study was to elucidate the possible role of CLA in ameliorating the pathophysiology in obese rats and modulate its immune function.Methods: Forty adult male albino rats of local strain, weighing [120-160] grams each, were used. Rats were ran-domly divided into five equal experimental groups, control, CLA-supplemented, obese, CLA-prophylactic obese and CLA-treated obese groups obesity was induced by High Fat Diet [HFD] for 12 weeks. CLA was administered orally in a dose of 1500mg/kg body weight for 12 weeks. Initial and final Body Weight (BW) and Body Mass Index (BMI) and food intake were measured. Total Leucocytic Count (TLC) and its differential count and serum Tumor Necrosis Factor-alpha (TNF-a) were measured. Visceral fat and total white abdominal fat to each 100 [gm]/BW were measured. Caspase 3 expression was evaluated in the abdominal fat biopsies using immuno-histochemistry.Results: High fat diet resulted in deterioration and impair-ment of most measured parameters. CLA supplementation decreased final BW of obese rats, food intake, visceral fat, and total abdominal together with increased CD8+, CD4+ T lymphocytes and eosinophilic %. Moreover, CLA supplemen-tation decreased TNF-a in CLA-supplemented and CLA-prophylactic groups but not in CLA-treated group. High fat diet increased TLC and CD4+ T lymphocytes but decrease eosinophilic % and CD8+ T lymphocytes. In addition, CLA increased the positivity of caspase 3 in CLA-prophylactics and CLA-treated obese groups.Conclusion: CLA supplementation, either as a prophylactic agent or a therapeutic one, to the high fat feed rats could ameliorate most of the detrimental effects of obesity, particu-larly those related to the immune system. This beneficial effect of CLA could be explained by its immune modulator, anti-inflammatory and pro apoptotic effects.

Cafeteria Diet Feeding in Young Rats Leads to Hepatic Steatosis and Increased Gluconeogenesis under Fatty Acids and Glucagon Influence.

Gluconeogenesis overstimulation due to hepatic insulin resistance is the best-known mechanism behind elevated glycemia in obese subjects with hepatic steatosis. This suggests that glucose production in fatty livers may differ from that of healthy livers, also in response to other gluconeogenic determinant factors, such as the type of substrate and modulators. Thus, the aim of this study was to investigate the effects of these factors on hepatic gluconeogenesis in cafeteria diet-induced obese adult rats submitted to a cafeteria diet at a young age. The livers of the cafeteria group exhibited higher gluconeogenesis rates when glycerol was the substrate, but lower rates were found when lactate and pyruvate were the substrates. Stearate or glucagon caused higher stimulations in gluconeogenesis in cafeteria group livers, irrespective of the gluconeogenic substrates. An increased mitochondrial NADH/NAD+ ratio and a reduced rate of 14CO2 production from [14C] fatty acids suggested restriction of the citric acid cycle. The higher glycogen and lipid levels were possibly the cause for the reduced cellular and vascular spaces found in cafeteria group livers, likely contributing to oxygen consumption restriction. In conclusion, specific substrates and gluconeogenic modulators contribute to a higher stimulation of gluconeogenesis in livers from the cafeteria group.

Optical assessment of changes in mechanical and chemical properties of adipose tissue in diet-induced obese rats.

Obesity is becoming a leading cause of health problems world-wide. Obesity and overweight are associated with the structural and chemical changes in tissues; however, few methods exist that allow for concurrent measurement of these changes. Using Brillouin and Raman microspectroscopy, both the mechanical and chemical differences can be assessed simultaneously. We hypothesized that Brillouin spectroscopy can measure the adipose tissues' stiffness, which increases in obesity. Samples of brown and white adipose tissues obtained from control and diet-induced obese adult rats were analyzed. The results show that both adipose tissues of the obese group exhibit a greater high-frequency longitudinal elastic modulus than the control samples, and that the brown fat is generally stiffer than white adipose. The Raman spectra indicate that the lipids' accumulation in adipose tissue outpaces the fibrosis, and that the high-fat diet has a greater effect on the brown adipose than the white fat. Overall, the powerful combination of Brillouin and Raman microspectroscopies successfully assessed both the mechanical properties and chemical composition of adipose tissue simultaneously for the first time. The results indicate that the adipose tissue experiences an obesity-induced increase in stiffness and lipid content, with the brown adipose tissue undergoing a more pronounced change compared to white adipose.

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats

Background/Aims: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. Methods: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. Results: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. Conclusions: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.

Dietary calcium supplementation in adult rats reverts brown adipose tissue dysfunction programmed by postnatal early overfeeding

Brown adipose tissue (BAT) dysfunction is associated with obesity and its comorbidities, such as hypertension, and the improvement of BAT function seems important for obesity management. Here we investigated the effects of dietary calcium supplementation on BAT autonomic nerve activity, sympathoadrenal function and cardiovascular parameters in adult obese rats that were raised in small litters (SL group). Three days after birth, SL litters were adjusted to three pups to induce early overfeeding. The control group remained with 10 pups/litter until weaning (NL group). At PN120, the SL group was randomly divided into the following: rats fed with standard chow (SL) and rats fed with dietary calcium carbonate supplementation (SL-Ca, 10g/kg chow). Animals were killed either at PN120 or PN180. At both ages, SL rats had higher BAT autonomic nervous system activity, mass and adipocyte area, as well as increased heart rate and blood pressure (systolic and diastolic); 2 months of calcium supplementation normalized these parameters. At PN180 only, UCP1 and TRβ1 in BAT were decreased in SL rats. These changes were also prevented by calcium treatment. Also at PN180, the SL group presented higher tyrosine hydroxylase and adrenal catecholamine contents, as well as lower hypothalamic POMC and MC4R contents. Calcium supplementation did not revert these alterations. Thus, we demonstrated that dietary calcium supplementation was able to improve cardiovascular parameters and BAT thermogenesis capacity in adult animals that were early overfed during lactation.

Early Treatment With Enalapril and Later Renal Injury in Programmed Obese Adult Rats.

Obesity-related kidney disease should be prevented or retarded. We aimed to investigate whether early treatment with enalapril ameliorates later renal injury induced by early postnatal overnutrition. Three or ten male pups per mother were assigned to either the Obese or Lean group during the first 21 days of life. These pups were treated with enalapril (Obese enalapril, OE; Lean enalapril, LE) or vehicle (Obese control, OC; Lean control, LC) for 15-28 days. Body weight, blood pressure (BP), and renal alterations were determined at 3 months. Enalapril decreased body weight only in the Lean group at 3 months (P < 0.05). Systemic BP levels were higher in the LE, OC, and OE groups than in the LC group at 3 months (P < 0.05). Fewer glomeruli per section area were found in the LE, OC, and OE groups than in the LC group and in the OE group than in the OC group (P < 0.05). The LE and OE groups had higher index scores of glomerulosclerosis and tubulointerstitial fibrosis than the controls (P < 0.05). LE pups showed increased intrarenal angiotensin II receptor type (AT)2 and matrix metalloproteinase (MMP)-9 and decreased renin and tissue inhibitor of MMP (TIMP)-1 expression than the LC rats (P < 0.05). OE pups showed increased intrarenal AT2 and decreased AT1 and TIMP-1 expression than the OC rats (P < 0.05). In conclusion, early treatment with enalapril can induce detrimental renal effects in later life and may not be renoprotective in programmed obese adult rats. J. Cell. Physiol. 232: 447-455, 2017. © 2016 Wiley Periodicals, Inc.

Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats.

Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity.

High calcium diet improves the liver oxidative stress and microsteatosis in adult obese rats that were overfed during lactation

Obesity is related to diabetes, higher oxidative stress and nonalcoholic fatty liver disease, and dietetic therapies, for instance calcium-rich diet, can improve these dysfunctions. Rats raised in small litters (SL) had increased fat depots and insulin resistance at adulthood associated with higher liver oxidative stress and microsteatosis. Thus, we evaluated if dietary calcium can improve these changes. In PN3, litter size was adjusted to 3 pups (SL group) to induce overfeeding, while controls had 10 pups until weaning. At PN120, SL group was randomly divided into: rats fed with standard chow or fed with calcium supplementation (SL–Ca group, 10 g/kg chow) for 60 days. At PN180, dietary calcium normalized food consumption, visceral fat, plasma aspartate aminotransferase (AST) and glycaemia. Concerning oxidative balance, calcium restored both higher hepatic lipid peroxidation and protein carbonylation as well as higher plasma lipid peroxidation. Higher fatty acid synthase (FAS) content, steatosis and lower protein kinase B (Akt) in SL group were normalized by dietary calcium and SL–Ca rats had lower hepatic cholesterol. Thus, calcium supplementation improved the insulin sensitivity, redox balance and steatosis in the liver. Therefore, dietary calcium can be a promising therapy for liver disease in the metabolic syndrome.