High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice

Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Endocrine (Impact Factor: 3.88). 05/2008; 33(2):176-88. DOI: 10.1007/s12020-008-9070-1
Source: PubMed

ABSTRACT We tested whether diet-induced obesity results from increased energy consumption, is associated with changes in expression of genes involved in leptin signal transduction, and is altered by hyperleptinemia. C57BL/6 mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for up to 15 weeks. HFD mice weighed significantly more than LFD controls by 3 weeks, despite consuming less energy. HFD mice had significantly greater leptin, insulin, and glucose levels than LFD mice, suggesting leptin and insulin resistance. Adiponectin levels declined with age but were unaffected by diet. HFD was associated with altered hypothalamic expression of genes whose products regulate the activity or nuclear translocation of STAT3, an important mediator of leptin actions. Expression of two isoforms of the leptin receptor decreased at 15 weeks in hypothalami of HFD mice in a tissue-specific manner. The type of fat (saturated versus unsaturated) did not influence weight gain on an HFD, but animals on LFD gained significantly more weight and adiposity if the dietary fat consisted mostly of saturated fats; this occurred despite no difference in energy consumption or absorption. Replacement of leptin to leptin-deficient ob/ob mice decreased hypothalamic leptin receptor expression and did not prevent HFD-induced weight gain. It is concluded that (1) increased energy consumption is not required for HFD-induced obesity in C57BL/6 mice, (2) HFD results in weight gain partly by modulating hypothalamic leptin-signaling pathways, (3) saturated fats induce weight gain even when total fat content of the diet is low, and (4) the effects of HFD are manifest in the presence or absence of circulating leptin.

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    • "Adiponectin is considered to be an anti-diabetic and anti-atherogenic hormone, but conflicting results on its levels in obese and diabetic patients and animal models have been shown in previous studies [24]. Some of them demonstrated declined circulating levels of adiponectin in high-fat diet fed rats [25] and mice [26] while others did not observe any changes [27,28]. A possible explanation for such difference is that the expression of adiponectin, could be altered by multiple factors including both genetic and environmental factors, as well as resting and fasting stages [29]. "
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    ABSTRACT: Background Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet. Methods Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan’s multiple range tests (DMRT) were used to determine the significant differences between groups. Results GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB). Conclusion Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.
    BMC Complementary and Alternative Medicine 12/2012; 12(1). DOI:10.1186/1472-6882-12-261 · 2.02 Impact Factor
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    • "It is known that high-fat diet (HFD) can cause overweight by resulting from a leptin resistance of the hypothalamic cells [11]. A deficiency of leptin, or a resistance of the hypothalamus to the actions of leptin, results in obesity in rodents and humans [5, 12]. It has been established that the lesion of the ventromedial hypothalamus causes hyperphagia and obesity, and lesion of the lateral hypothalamus causes aphagia and even death by starvation [11]. "
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    ABSTRACT: It has been demonstrated that the type of diet affects the brain structure and function. Consumption of fat-rich food is one of the most important factors that lead to increase in the prevalence of cardiovascular and neurological diseases. High-fat diet may change the volume and neuronal number or density in the hypothalamus, which is the center of energy control. Therefore, this study was designed to study the effect of high-fat diet on the density and number of neurons, and also the volume of hypothalamus in adult male mice. Forty male mice were divided into the control and experimental groups. The control group were fed with standard and the experimental groups, with high-fat diet for 4 (short-term) or 8 (long-term) weeks. The animals were perfused and brains were immediately removed, post-fixed and cut coronally and serially using cryostat at 30-µm thickness. Every 6th sections were stained by cresyl violet. The numerical density and number of neuron and the volume of hypothalamus were estimated by using unbiased stereological methods. Data analysis showed that both short and long time consumption of high-fat diet decreased the neuronal cell density of the hypothalamus. Interestingly, despite a decrease in the neuronal cell density, long time consumption of high-fat diet could significantly increase the volume of hypothalamus (P<0.05). High fat diet decreased the neuronal cell density and increased the volume of the hypothalamus, but it did not significantly change its total neurons. These changes might be due to an increase in the extracellular space through inflammation or gliosis in the hypothalamus.
    Anatomy & cell biology 09/2012; 45(3):178-84. DOI:10.5115/acb.2012.45.3.178
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    • "Some studies indicate that impairment on mitochondrial metabolism may lead to excessive body weight gain when the subjects are fed with high-calorie western diets.44 The study of Townsend et al45 offered two different diets (hyperlipidic and hypolipidic) to rats, both diets predominant in saturated fat. The animals which consumed a high-fat diet, despite featuring lower total energy intake, had increased body fat more than the low-fat diet group, and had a higher weight gain even with increased leptin levels, pointing to the mechanism of leptin resistance. "
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    ABSTRACT: Studies have been conducted in order to identify the main factors that contribute to the development of obesity. The role of genetics has also been extensively studied. However, the substantial augmentation of obesity prevalence in the last 20 years cannot be justified only by genetic alterations that, theoretically, would have occurred in such a short time. Thus, the difference in obesity prevalence in various population groups is also related to environmental factors, especially diet and the reduction of physical activity. These aspects, interacting or not with genetic factors, could explain the excess of body fat in large proportions worldwide. This article will focus on positive energy balance, high-fat diet, alteration in appetite control hormones, insulin resistance, amino acids metabolism, and the limitation of the experimental models to address this complex issue.
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 04/2012; 5:75-87. DOI:10.2147/DMSO.S25026
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