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

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.

LIM-homeodomain Transcription Factor Isl-1 Mediates the Effect of Leptin on Insulin Secretion in Mice

“…To study the effect of the global serum leptin on Isl-1 expression, adult male mice were randomly divided into the high fat diet (HFD), the regular grain diet control, and fasted mice (n Ն 6 for each group) as previous reported (27,28), the HFD and control groups were fed 24 h, and the fasted group was starved for 24 h. The procedures for blood and tissue collections were similar to our previous report (29).…”

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

“…It is now evident that environmentally induced alterations of multiple organ systems, most prominently the central nervous system (CNS), contribute to these predisposing pathologies (reviewed in [7][8][9][10][11][12][13][14][15][16][17]). Respecting fuel metabolism, insulin resistance is generally characterized by a diminished ability of insulin to (1) stimulate glucose uptake in tissues responsive to such insulin action, (2) inhibit glucose production and stimulate glucose storage in liver, (3) inhibit lipolysis in adipose tissue, and (4) promote vascular relaxation and health [1][2][3][4][5][6]18,19].…”

Sixteen years and counting: an update on leptin in energy balance

“…However, for reasons that are not fully understood, obese individuals do not show diminished appetite and increased energy expenditure, as would be predicted based on their increased leptin levels (6,31). Likewise, in animal models, high-fat diet-induced hyperleptinemia aggravates weight gain and metabolic anomalies (32)(33)(34). In the face of these observations, researchers elaborated the concept of leptin resistance, which refers to the inability of obese individuals and high-fat-fed animals to respond to endogenous or exogenous leptin (35).…”