The effect of weight loss on whole‐body and tissue‐specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy

Abstract

Objective This study (1) investigated the effect of weight loss on whole‐body and tissue‐specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight‐loss‐induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity. Methods In this secondary analysis of the European SWEET project, 50 adults (age 18–65 years) with overweight or obesity (BMI ≥ 25 kg/m2) followed a low‐energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual‐energy x‐ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole‐body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7‐point oral glucose tolerance test). Results The LED reduced body weight (p < 0.001). This was accompanied by increased Matsuda index and reduced HIRI (both p < 0.001) but no change in MISI (p = 0.260). Weight loss decreased IHL content (mean [SEM], 3.9% [0.7%] vs. 1.6% [0.5%], p < 0.001) and the hepatic saturated fatty acid fraction (41.0% [1.5%] vs. 36.6% [1.9%], p = 0.039). The reduced IHL content was associated with an improvement in HIRI (r = 0.402, p = 0.025). Conclusions Weight loss decreased IHL content and the hepatic saturated fatty acid fraction. The decrease in IHL content was associated with weight‐loss‐induced improvement in hepatic insulin sensitivity in individuals with overweight or obesity.

Lipid-encapsulated mRNA encoding an extended serum half-life interleukin-22 ameliorates metabolic disease in mice

“…In summary, reduction in hepatic expression of genes involved in fibrosis and lipogenesis was observed. These effects could be driven by direct effects of IL-22 on activity of these pathways [ 73 , 74 ] or be the result of reduced food intake and body weight, which could consequently improve insulin resistance, lipogenesis, and general metabolic health [ 75 ].…”