Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction

Metabolism. 2013 Apr;62(4):595-603. doi: 10.1016/j.metabol.2012.10.010. Epub 2012 Nov 20.

Abstract

Objective: The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity.

Materials/methods: Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate).

Results: Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3±1.3kg (p<0.0001 compared with eucaloric). Whole-body insulin sensitivity was unchanged after calorie restriction and similar between groups. However, ex vivo skeletal muscle insulin signalling differed depending on macronutrient composition of calorie-restricted diet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity.

Conclusion: Acute caloric restriction with an LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with an HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / physiology
  • Blotting, Western
  • Caloric Restriction*
  • Diet*
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Female
  • Glucose Clamp Technique
  • Humans
  • Insulin / physiology*
  • Insulin Receptor Substrate Proteins / physiology
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Muscle, Skeletal / physiology*
  • Obesity / physiopathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Signal Transduction / physiology*
  • Young Adult

Substances

  • Blood Glucose
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphatidylinositol 3-Kinases