scholarly journals Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring

2007 ◽  
Vol 293 (3) ◽  
pp. R1056-R1062 ◽  
Author(s):  
Jacqueline Férézou-Viala ◽  
Anne-France Roy ◽  
Colette Sérougne ◽  
Daniel Gripois ◽  
Michel Parquet ◽  
...  

Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (−12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.

2016 ◽  
Vol 36 (5) ◽  
pp. 483-493 ◽  
Author(s):  
AO Abolaji ◽  
IO Awogbindin ◽  
IA Adedara ◽  
EO Farombi

The fungicide carbendazim (CBZ) and insecticide chlorpyrifos (CPF) are currently applied together by farmers for the control of pests. Here, we investigated the impacts of 7 days oral co-exposure to 10 mg/kg body weight of CPF and 50 mg/kg body weight of CBZ on selected oxidative stress and antioxidant biomarkers in the liver, kidney, and spleen of female rats. The results showed that while the body weight gain and relative organ weights were not significantly affected after separate exposure to CPF and CBZ, there was a significant decrease in the body weight gain with concomitant increases in the relative kidney and spleen weights of rats treated with the mixture. Also, CPF and CBZ co-exposure significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine ( p < 0.05) when compared with the groups treated with CBZ or CPF alone and the control. The significant decreases in both antioxidant enzymes activities and nonenzymatic antioxidant level following individual administration of CPF and CBZ to rats were intensified in the co-exposure group ( p < 0.05). Additionally, the marked increases in the levels of oxidative stress indices in liver, kidney, and spleen of rats treated with CPF or CBZ alone were intensified in the co-exposure group ( p < 0.05). Histopathologically, co-exposure to CPF and CBZ exacerbates their individual effects on the liver, kidney, and spleen. These findings showed that co-exposure to CPF and CBZ in rats elicited more severe oxidative damage on the liver, kidney, and spleen of the rats, indicative of an additive effect compared to CPF or CBZ alone and as such, may pose a greater environmental risk to humans.


2020 ◽  
Vol 70 (2) ◽  
pp. 144-151
Author(s):  
María del Rocío Padilla Galindo ◽  
Alma Gabriela Martínez Moreno ◽  
Fatima Ezzahra Housni ◽  
Zyanya Reyes Castillo ◽  
Erika Saenz-Pardo Reyes

El consumo de stevia ha sido promovido por su bajo aporte calórico, su efecto antidiabético y antihipercolesterolémico. Sin embargo, los efectos de la ingesta de stevia parecen no ser los mismos para las ratas hembras respecto de los machos. El propósito de este estudio fue evaluar el efecto de la ingesta de stevia sobre el consumo de alimento, peso corporal y niveles de glucosa, insulina, colesterol y triglicéridos en ratas hembras Wistar durante 13 semanas y realizar un análisis predictivo del peso corporal y la ingesta de alimento a 20 semanas. Se utilizaron 20 ratas hembras adultas, que se dividieron en 2 grupos: control (CG) y stevia (SG), ambos grupos recibieron agua y comida a libre acceso, así como una solución de stevia al 0,2 % para el grupo SG. Se registró diariamente el consumo de alimento, agua y solución de stevia; la medición del peso corporal se realizó semanalmente. Al final de las 13 semanas de experimentación, los animales se sacrificaron para evaluar los parámetros metabolicos. El grupo SG mostró un mayor consumo de alimento, mayor proporción de ganancia de peso corporal, niveles de glucosa y colesterol que el grupo CG. No se encontraron diferencias significativas en los niveles de triglicéridos e insulina. Respecto al análisis predictivo (semanas 14-20), se mantiene un incremento significativo en el consumo de alimento y se observa una tendencia de aumento en la proporción de ganancia de peso corporal. Esto indica que el consumo de stevia en ratas hembras parece no tener los mismos efectos benéficos reportados en machos. Consumption of stevia has been promoted due to its low caloric intake, it’s effects as anti-diabetic and anti-hypercholesterolemic. However, the effects of stevia consumption is apparently not the same in females than males. The purpose of this study was to evaluate the effect of stevia intake on meal consumption, body weight and levels of glucose, insulin, cholesterol and triglycerides in female Wistar rats during 13 weeks and develop a predictive analysis of the body weight and meal intake over 20 weeks. 20 adult female rats were utilized, these were divided into two groups: control (CG) and stevia (SG), both groups received free access to water and food, the SG also received a stevia solution at 0.2%. Consumption of food, water and stevia solution was recorded daily, while weight was recorded weekly. At the end of the 13 weeks of experiment, the subjects were sacrificed to evaluate the metabolic parameters. The SG group showed a higher consumption of food, higher proportion of body weight gain, glucose levels and cholesterol than the CG. No significant differences were found in levels of triglyceride or insulin. Respect to the predictive analysis (weeks 14-20), a significant increase in food consumption is maintained and an increasing trend is observed in the proportion of body weight gain. This indicates that stevia consumption appears not to have the same benefit effects in female rats than male rats.


2011 ◽  
Vol 107 (9) ◽  
pp. 1245-1248 ◽  
Author(s):  
Nicolas Desbuards ◽  
Pascal Gourbeyre ◽  
Vianney Haure-Mirande ◽  
Dominique Darmaun ◽  
Martine Champ ◽  
...  

To assess the impact of prebiotic supplementation during gestation and fetal and early neonatal life, gestating BALB/cj dam mice were fed either a control or a prebiotic (galacto-oligosaccharides–inulin, 9:1 ratio)-enriched diet throughout pregnancy and lactation, and allowed to nurse their pups until weaning. At the time of weaning, male offspring mice were separated from their mothers, weaned to the same solid diet as their dam and their growth was monitored until killed 48 d after weaning. Prebiotic treatment affected neither the body-weight gain nor the food intake of pregnant mice. In contrast, at the time of weaning, pups that had been nursed by prebiotic-fed dams had a higher body weight (11·0 (se 1·2) g) than pups born from control dams (9·8 (se 0·9) g). At 48 d after weaning, significantly higher values were observed for colon length and muscle mass in the offspring of prebiotic-fed dams (1·2 (se 0·1) cm/cm and 5·7 (se 1·8) mg/g, respectively), compared with control offspring (1·1 (se 0·1) cm/cm and 2·9 (se 0·9) mg/g, respectively), without any difference in spleen and stomach weight, or serum leptin concentration. The present preliminary study suggests that altering the fibre content of the maternal diet during both pregnancy and lactation enhances offspring growth, through an effect on intestinal and muscle mass rather than fat mass accretion.


2019 ◽  
Vol 317 (2) ◽  
pp. E337-E349
Author(s):  
Elizabeth T. Nguyen ◽  
Sarah Berman ◽  
Joshua Streicher ◽  
Christina M. Estrada ◽  
Jody L. Caldwell ◽  
...  

Psychological stress and excess glucocorticoids are associated with metabolic and cardiovascular diseases. Glucocorticoids act primarily through mineralocorticoid (MR) and glucocorticoid receptors (GR), and compounds modulating these receptors show promise in mitigating metabolic and cardiovascular-related phenotypes. CORT118335 (GR/MR modulator) prevents high-fat diet-induced weight gain and adiposity in mice, but the ability of this compound to reverse obesity-related symptoms is unknown. Adult male rats were subcutaneously administered CORT118335 (3, 10, or 30 mg/kg) or vehicle once daily. A 5-day treatment with CORT118335 at 30 mg/kg induced weight loss in rats fed a chow diet by decreasing food intake. However, lower doses of the compound attenuated body weight gain primarily because of decreased calorific efficiency, as there were no significant differences in food intake compared with vehicle. Notably, the body weight effects of CORT118335 persisted during a 2-wk treatment hiatus, suggesting prolonged effects of the compound. To our knowledge, we are the first to demonstrate a sustained effect of combined GR/MR modulation on body weight gain. These findings suggest that CORT118335 may have long-lasting effects, likely due to GR/MR-induced transcriptional changes. Prolonged (18 days) treatment of CORT118335 (10 mg/kg) reversed body weight gain and adiposity in animals fed a high-fat diet for 13 wk. Surprisingly, this occurred despite a worsening of the lipid profile and glucose homeostasis as well as a disrupted diurnal corticosterone rhythm, suggesting GR agonistic effects in the periphery. We conclude that species and tissue-specific targeting may result in promising leads for exploiting the metabolically beneficial aspects of GR/MR modulation.


2010 ◽  
Vol 31 (4) ◽  
pp. 600-601 ◽  
Author(s):  
Christa M. Patterson ◽  
Sebastien G. Bouret ◽  
Sunny Park ◽  
Boman G. Irani ◽  
Ambrose A. Dunn-Meynell ◽  
...  

Abstract Because rearing rats in large litters (LLs) protects them from becoming obese, we postulated that LL rearing would protect rats selectively bred to develop diet-induced obesity (DIO) from becoming obese by overcoming their inborn central leptin resistance. Male and female DIO rats were raised in normal litters (10 pups/dam) or LLs (16 pups/dam) and assessed for anatomical, biochemical, and functional aspects of leptin sensitivity at various ages when fed low-fat chow or a 31% fat high-energy (HE) diet. LL rearing reduced plasma leptin levels by postnatal d 2 (P) 2 and body weight gain by P8. At P16, LL DIO neonates had increased arcuate nucleus (ARC) binding of leptin to its extracellular receptors and at P28 an associated increase of their agouti-related peptide and α-MSH axonal projections to the paraventricular nucleus. Reduced body weight persisted and was associated with increased ARC leptin receptor binding and sensitivity to the anorectic effects of leptin, reduced adiposity, and enhanced insulin sensitivity in LL DIO rats fed chow until 10 wk of age. The enhanced ARC leptin receptor binding and reduced adiposity of LL DIO rats persisted after an additional 5 wk on the HE diet. Female LL DIO rats had similar reductions in weight gain on both chow and HE diet vs. normal litter DIO rats. We postulate that LL rearing enhances DIO leptin sensitivity by lowering plasma leptin levels and thereby increasing leptin receptor availability and that this both enhances the ARC-paraventricular nucleus pathway development and protects them from becoming obese.


2008 ◽  
Vol 295 (4) ◽  
pp. E895-E903 ◽  
Author(s):  
Malathi Srinivasan ◽  
Catherine Dodds ◽  
Husam Ghanim ◽  
Tao Gao ◽  
Peter J. Ross ◽  
...  

Our earlier studies have shown that the artificial rearing of newborn rat pups [first generation high carbohydrate (1-HC)] on an HC milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring [second-generation HC (2-HC)] of 1-HC female rats spontaneously acquired the HC phenotype in the postweaning period. In this study, we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on laboratory chow and increased body weight gain beginning from the immediate postweaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain and increased plasma levels of insulin, leptin, proinflammatory markers, and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with those of control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring.


2011 ◽  
Vol 34 (8) ◽  
pp. 1257-1263 ◽  
Author(s):  
Takahiro Hayashi ◽  
Yuriko Nozaki ◽  
Makoto Nishizuka ◽  
Masahito Ikawa ◽  
Shigehiro Osada ◽  
...  

2007 ◽  
Vol 293 (5) ◽  
pp. R1855-R1863 ◽  
Author(s):  
Christine Mack ◽  
Julie Wilson ◽  
Jennifer Athanacio ◽  
James Reynolds ◽  
Kevin Laugero ◽  
...  

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4–11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3–300 μg·kg−1·day−1) dose dependently reduced food intake and body weight gain (ED50for body weight gain = 16.5 μg·kg−1·day−1). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 μg·kg−1·day−1) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 μg·kg−1·day−1) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Mohammed A Khan ◽  
Preethi Samuel ◽  
Sourashish Nag ◽  
Tahir Hussain

Obesity in itself is a disease condition and a major risk factor in the development of hypertension, dyslipidemia, and hyperglycemia. Therefore, successful strategies for improving obesity and related metabolic risk factors are needed. Role of renin-angiotensin system (RAS) has been implicated in obesity and metabolic dysfunction. Recently, we have shown that AT2R knock-out in female mice caused a greater body weight gain and hyperinsulimia in response to high fat diet (HFD). In the present study, we hypothesize that AT2R activation rescues diet-induced obesity in females. To test this hypothesis, we injected AT2R non-peptide agonist C21 (0.3mg/kg/day i.p) in C57BL6 female mice on HFD for 12 weeks. C21-treatment did not affect the HFD calorie intake (HFD: 937±18 Kcal; C21HFD: 886±37 Kcal) but caused lesser body weight gain compared to control (HFD: 4.4± 0.4g; C21HFD: 3.06± 0.4g). Similar to the body weight gain pattern, gonadal fat weight and adipocyte size were decreased significantly in C21-treated mice on HFD compared to control HFD group (HFD: 4.4± 0.4 g; C21 HFD: 3.06± 0.4g) and (HFD: 6404±161.6μm2 ; C21HFD: 3874±103.2μm2 ) respectively. Moreover, the C21-treated females on HFD had lower levels of plasma insulin, improved glucose tolerance, and decreased plasma free fatty acids and hepatic triglycerides. Western blot revealed that phospho-Ser79-acetyl CoA carboxylase (p-Ser79-ACC-1) was reduced, an index of increased lipogenic activity and decreased β-oxidation process, in both adipose (Adi) and hepatic (Hep) tissues of HFD fed groups (Adi: 86% and Hep: 73% of 100% controls); C21-treatment revered the decrease in p-ser79-ACC-1 in Adi (104% of control) and caused an increase in Hep (122% of control) respectively. The HFD feeding lowered the estradiol level (ND: 38.8±2.6 vs HFD:11.3±1.2ng), which was modestly reversed by C21 treatment (C21HFD:17.4± 1.5ng) in HFD mice. Our results strongly suggest that stimulation of AT2R in female mice positively contribute, predominantly independent of estrogen, to rescue body weight gain and adipocyte size increase in response to HFD. We propose reduced lipogenesis and enhanced lipid β-oxidation as potential mechanisms linked to AT2R action in reducing obesity and its related metabolic disorders in females.


2016 ◽  
Vol 85 (1) ◽  
pp. 99-104
Author(s):  
Branislav Gálik ◽  
Daniel Bíro ◽  
Milan Šimko ◽  
Miroslav Juráček ◽  
Marcela Capcarová ◽  
...  

The aim of this study was to analyse the effects of different daily intakes of rapeseed bee pollen on the growth and biochemical blood serum indicators in male and female rats. A total of 40 clinically healthy male and female Wistar rats were randomly divided into four groups. In the control group (C) rats were fed a standard complete diet; in the experimental groups standard diets were supplemented with different doses of bee pollen. Treatment group T1 was given standard diet with the addition of bee pollen at a 0.3% concentration; in group T2 the addition was 0.5%; and in group T3 it was 0.75%. The experimental period lasted for 90 days. A significant effect (P < 0.05) of bee pollen on the body weight gain and feed conversion ratio of female rats was found. Significantly (P < 0.05) higher cholesterol concentration in blood serum of male rats was found in the groups with bee pollen addition (groups T2 and T3) compared to the control group. Lower triglyceride serum content in all female experimental groups (T1 and T3) was observed in comparison to the control. Higher serum cholesterol content in the experimental female rats was detected; significant differences were analysed in groups T1 and T3 compared to the control female group. Rapeseed bee pollen at concentrations of 0.5 and 0.75% positively affected the body weight gain of female rats, however, with higher feed consumption (P < 0.05). Rapeseed bee pollen reduced the triglycerides serum content in female rats and increased the cholesterol serum content in male and female rats (P < 0.05).


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