Selective Inactivation of Socs3 in SF1 Neurons Improves Glucose Homeostasis without Affecting Body Weight

Suppressor of cytokine signaling 3 (Socs3) has been identified as a mediator of central leptin resistance, but the identity of specific neurons in which Socs3 acts to suppress leptin signaling remains elusive. The ventromedial hypothalamus (VMH) was recently shown to be an important site for leptin action because deleting leptin receptor within VMH neurons causes obesity. To examine the role of VMH Socs3 in leptin resistance and energy homeostasis, we generated mice lacking Socs3 specifically in neurons positive for steroidogenic factor 1 (SF1), which is expressed abundantly in the VMH. These mice had increased phosphorylation of signal transducer and activator of transcription-3 in VMH neurons, suggesting improved leptin signaling, and consistently, food intake and weight-reducing effects of exogenous leptin were enhanced. Furthermore, on either chow or high-fat diets, these mice had reduced food intake. Unexpectedly, energy expenditure was reduced as well. Mice lacking Socs3 in SF1 neurons, despite no change in body weight, had improved glucose homeostasis and were partially protected from hyperglycemia and hyperinsulinemia induced by high-fat diets. These results suggest that Socs3 in SF1 neurons negatively regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure.

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Eisenia bicyclis Inhibits Body Weight Gain and Fat Accumulation Induced by High-Fat Diets in Mice

Preventive Nutrition and Food Science ◽

10.3746/jfn.2010.15.4.262 ◽

2010 ◽

Vol 15 (4) ◽

pp. 262-266 ◽

Cited By ~ 2

Author(s):

Won-Hee Choi ◽

Ji-Yun Ahn ◽

Sun-A Kim ◽

Tae-Wan Kim ◽

Tae-Youl Ha

Keyword(s):

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

High Fat ◽

Eisenia Bicyclis ◽

Fat Accumulation ◽

High Fat Diets ◽

Fat Diets

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Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

Journal of Endocrinology ◽

10.1530/joe-13-0526 ◽

2014 ◽

Vol 221 (3) ◽

pp. 381-390 ◽

Cited By ~ 21

Author(s):

Gustavo W Fernandes ◽

Cintia B Ueta ◽

Tatiane L Fonseca ◽

Cecilia H A Gouveia ◽

Carmen L Lancellotti ◽

...

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Liver Steatosis ◽

Mrna Levels ◽

High Fat ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

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Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000154 ◽

2014 ◽

Vol 5 (3) ◽

pp. 229-239 ◽

Cited By ~ 10

Author(s):

K. M. Platt ◽

R. J. Charnigo ◽

K. J. Pearson

Keyword(s):

Body Composition ◽

Body Weight ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

High Fat Diet ◽

High Fat ◽

High Fat Diets ◽

Normal Glucose ◽

Fat Diets

Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10–11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10–11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.

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Development of leptin resistance in rat soleus muscle in response to high-fat diets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.6.e1374 ◽

2000 ◽

Vol 279 (6) ◽

pp. E1374-E1382 ◽

Cited By ~ 81

Author(s):

Greg R. Steinberg ◽

David J. Dyck

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Soleus Muscle ◽

Leptin Resistance ◽

Safflower Oil ◽

High Fat ◽

Muscle Lipid ◽

High Fat Diets ◽

Rat Soleus Muscle ◽

Fat Diets

Direct evidence for leptin resistance in peripheral tissues such as skeletal muscle does not exist. Therefore, we investigated the effects of different high-fat diets on lipid metabolism in isolated rat soleus muscle and specifically explored whether leptin's stimulatory effects on muscle lipid metabolism would be reduced after exposure to high-fat diets. Control (Cont, 12% kcal fat) and high-fat [60% kcal safflower oil (n-6) (HF-Saff); 48% kcal safflower oil plus 12% fish oil (n-3)] diets were fed to rats for 4 wk. After the dietary treatments, muscle lipid turnover and oxidation in the presence and absence of leptin was measured using pulse-chase procedures in incubated resting soleus muscle. In the absence of leptin, phospholipid, diacylglycerol, and triacylglycerol (TG) turnover were unaffected by the high-fat diets, but exogenous palmitate oxidation was significantly increased in the HF-Saff group. In Cont rats, leptin increased exogenous palmitate oxidation (21.4 ± 5.7 vs. 11.9 ± 1.61 nmol/g, P = 0.019) and TG breakdown (39.8 ± 5.6 vs. 27.0 ± 5.2 nmol/g, P = 0.043) and decreased TG esterification (132.5 ± 14.6 vs. 177.7 ± 29.6 nmol/g, P = 0.043). However, in both high-fat groups, the stimulatory effect of leptin on muscle lipid oxidation and hydrolysis was eliminated. Partial substitution of fish oil resulted only in the restoration of leptin's inhibition of TG esterification. Thus we hypothesize that, during the development of obesity, skeletal muscle becomes resistant to the effects of leptin, resulting in the accumulation of intramuscular TG. This may be an important initiating step in the development of insulin resistance common in obesity.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00117.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. R1056-R1062 ◽

Cited By ~ 123

Author(s):

Jacqueline Férézou-Viala ◽

Anne-France Roy ◽

Colette Sérougne ◽

Daniel Gripois ◽

Michel Parquet ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

Maternal Diet ◽

The Body ◽

Female Rats ◽

Leptin Resistance ◽

High Fat ◽

Leptin Sensitivity ◽

The Impact

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.

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Effect of high fat diets on the performance and food intake of primiparous and multiparous rabbit does

Animal Science ◽

10.1017/s1357729800009668 ◽

1998 ◽

Vol 66 (2) ◽

pp. 491-499 ◽

Cited By ~ 25

Author(s):

J. J. Pascual ◽

C. Cervera ◽

E. Blas ◽

J. Fernandez-Carmona

Keyword(s):

Food Intake ◽

Control Diet ◽

Live Weight ◽

Production Traits ◽

High Fat ◽

Protein Ratio ◽

Weight Losses ◽

High Fat Diets ◽

Digestible Protein ◽

Fat Diets

AbstractThe influence of high fat diets on several production traits of primiparous and multiparous rabbit does was studied in 246 lactations from a total of 61 crossbreed rabbit does (Californian × New Zealand). Starting with a control diet (diet C) with 26 g ether extract (EE) per kg dry matter (DM), two isoenergetic diets were formulated adding fat from vegetable sources up to 99 g EE per kg DM (diet V) or animal sources up to 117 g EE per kg DM (diet A). Digestible energy/digestible protein ratio (DE/DP) was maintained between 82 and 87 kj/g. Food intake decreased with high fat diets compared with the control diet during gestation (P ‘lt; 0·001), which implied a decrease in the DE intake (P < 0·01 and P < 0·05 for primiparous and multiparous does, respectively). Fat addition did not affect food intake of primiparous does during lactation (101·8,106·9 and 103·7 g DM per day per kg live weight (M)0·75 for C, V and A diets, respectively) but increased the DE intake (1121 kj/day per kg M°0·75 for C diet cf. 1325 for V and 1264 for A diets; P < 0·01) and reduced does' weight losses at the end of lactation (F > 0·05). However, multiparous does on C diet showed a greater food intake during the last 2 weeks of lactation (110·6 for C diet v. 101·5 and 98·9 g DM per day per kg M0·75 for V and A diets, respectively; P < 0·001). High fat diets improved significantly the productive parameters at the 21st day of lactation: increasing litter size (P < 0·01 for multiparous does) and weight (P < 0·01 and P < 0·001 for primiparous and multiparous does, respectively) and decreasing the food conversion ratio (P < 0·001). An increase of dietary fat content decreased solid food intake of litters during the last 2 weeks of lactation (P < 0·01 and P < 0·001 for primiparous and multiparous does, respectively) but only affected their solid DE intake slightly. In conclusion, high fat diets seem to improve the productivity of lactating does and their corporal condition during the first lactation.

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Effect of nutrition on growth and somatomedin A levels in the rat

Acta Endocrinologica ◽

10.1530/acta.0.0940321 ◽

1980 ◽

Vol 94 (3) ◽

pp. 321-326 ◽

Cited By ~ 9

Author(s):

Kazue Takano ◽

Naomi Hizuka ◽

Kazuo Shizume ◽

Yoko Hasumi ◽

Toshio Tsushima

Keyword(s):

Growth Hormone ◽

Body Weight ◽

Normal Growth ◽

Protein Diet ◽

Low Protein Diet ◽

High Fat ◽

Low Protein ◽

High Fat Diets ◽

Hypophysectomized Rats ◽

Fat Diets

Abstract. Serum somatomedin A was significantly reduced after 3 days of fasting in rats with a mean decrease of 23.6 ± 2.4% (N = 18) of initial values. Re-feeding for one day produced a definite increase in somatomedin A, with a rise in body weight. When re-fed isocalorically for 21 days with diets of different quality, a low protein diet led to smaller increases in both seum somatomedin A and body weight in comparison to those of control-, high-protein- and high fat-diets (P < 0.001). There is a positive correlation between the increase in body weight and serum somatomedin A levels (N = 70, r = 0.71, P< 0.001). The effect of growth hormone on somatomedin generation was abolished in hypophysectomized rats fed with low-protein diet. Our study suggests that protein in the diet is important for the generation of somatomedin A, which is necessary for normal growth.

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Oat bran β-glucan improves glucose homeostasis in mice fed on a high-fat diet

RSC Advances ◽

10.1039/c7ra10437e ◽

2017 ◽

Vol 7 (86) ◽

pp. 54717-54725 ◽

Cited By ~ 3

Author(s):

Yuliang Cheng ◽

Jie Zhang ◽

Kaiyun Luo ◽

Genyi Zhang

Keyword(s):

Body Weight ◽

Food Intake ◽

Glucose Homeostasis ◽

High Fat Diet ◽

High Fat ◽

Low Fat ◽

Oat Bran

The changes of body weight (A) and food intake (B) of mice fed on different diets of low-fat (LF), high-fat (HF), HF + grain form β-glucan (HFGF), and HF + extracted β-glucan (HFEX).

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