Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction

Abstract

Background & aims: We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity.

Methods: Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (<50 g/day) energy-deficit diet. A euglycemic-hyperinsulinemic clamp, muscle biopsy specimens, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling, and intrahepatic triglyceride (IHTG) content before, after 48 hours, and after approximately 11 weeks (7% weight loss) of diet therapy.

Results: At 48 hours, IHTG content decreased more in the LC than the HC diet group (29.6% +/- 4.8% vs 8.9% +/- 1.4%; P < .05) but was similar in both groups after 7% weight loss (LC diet, 38.0% +/- 4.5%; HC diet, 44.5% +/- 13.5%). Basal glucose production rate decreased more in the LC than the HC diet group at 48 hours (23.4% +/- 2.2% vs 7.2% +/- 1.4%; P < .05) and after 7% weight loss (20.0% +/- 2.4% vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05).

Conclusions: Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

Figures

Figure 1

Changes in body composition and intrahepatic triglyceride (IHTG) content after 48 h (2% weight loss) and ~11 weeks (7% weight loss) of calorie restriction in obese subjects consuming either a high-carbohydrate or low-carbohydrate 1000 kcal/d deficit diet. Values are means ± SEM. Value significantly different from baseline value; *P#Value significantly different from corresponding high-carbohydrate diet group, P<0.05. FM=Fat Mass, FFM= Fat-free Mass

Figure 2

Relative changes in basal glucose Rate of appearance (Ra) in plasma after 48 h of calorie restriction and 7% weight loss. Values are means ± SEM. *Value significantly different from baseline value; P# Value significantly different from value in AC group; P<0.001.

Figure 3

Hepatic insulin sensitivity index (HISI) (top panel) in subjects consuming ether a high-carbohydrate or low-carbohydrate diet and changes in insulin mediated glucose uptake, an index of skeletal muscle insulin sensitivity, in both groups combined (bottom panel) after 48 h and ~11 wks (7% weight loss) of calorie restriction. Value significantly different from baseline value: * P# P<0.05.

Figure 3

Hepatic insulin sensitivity index (HISI) (top panel) in subjects consuming ether a high-carbohydrate or low-carbohydrate diet and changes in insulin mediated glucose uptake, an index of skeletal muscle insulin sensitivity, in both groups combined (bottom panel) after 48 h and ~11 wks (7% weight loss) of calorie restriction. Value significantly different from baseline value: * P# P<0.05.

Figure 4

Changes in phosphoTyr183 JNK, phosphoTyr IRS, and phosphoSer473 Akt/PKB protein levels in vastus lateralis muscle biopsies obtained after 30 min of insulin infusion during a euglycemic-hyperinsulinenmic clamp procedure after 48 h and ~11 wks (7% weight loss) of calorie restriction. Values are corrected for total JNK, IRS1, and Akt/PKB protein content and normalized (=0) to values from baseline samples (day 0). Values are means± SEM. Value significantly different from corresponding baseline value, *p