Faculty Opinions recommendation of Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding.

The study investigated whether a persistent impairment of insulin secretion resulting from mild protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of the diabetogenic challenge of high-fat feeding. Offspring of dams provided with either control (20% protein) diet (C) or an isocaloric restricted (8%) protein diet (PR) were weaned onto the maintenance diet with which their mothers had been provided. At 20 wk of age, protein restriction enhanced glucose tolerance despite impaired insulin secretion and an augmented and sensitized lipolytic response to norepinephrine in adipocytes. C and PR rats were then transferred to a high-fat diet (HF, 19% protein, 22% lipid, 34% carbohydrate) and sampled after 8 wk. These groups are termed C-HF and PR-HF. Glucose tolerance was impaired in PR-HF, but not C-HF, rats. Insulin-stimulated glucose disposal rates were significantly lower (by 30%; P < 0.01) in the PR-HF group than in the C-HF group, and a specific impairment of antilipolytic response of insulin was unmasked in adipocytes from PR-HF, but not C-HF, rats. The study demonstrates that antecedent protein restriction accelerates and augments the development of impaired glucoregulation and insulin resistance after high-fat feeding.

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Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00251.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. E30-E39 ◽

Cited By ~ 61

Author(s):

So-Young Park ◽

Hyo-Jeong Kim ◽

Shupei Wang ◽

Takamasa Higashimori ◽

Jianying Dong ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Metabolism ◽

Insulin Action ◽

Hormone Sensitive Lipase ◽

Wild Type ◽

High Fat ◽

Hormone Sensitive ◽

Fat Feeding

Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50–80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism.

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