Abstract
Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography–time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus, dietary leucine supplementation may potentially be a nutritional intervention to attenuate hepatic steatosis and early DN in type II diabetes.
Highlights
Type 2 diabetes mellitus (T2DM) has emerged as one of the most severe health concerns in the world
The db/db mice exhibited higher levels of blood glucose compared with other groups; levels were reduced by dietary leucine supplementation (Figure 1C)
Leucine supplementation had no obvious influence on the body weight neither in control mice nor in db/db mice over a 12-week-period
Summary
Type 2 diabetes mellitus (T2DM) has emerged as one of the most severe health concerns in the world. The longitudinal progression of obesity, insulin resistance, metabolic syndrome, T2DM, and T2DM-associated complications, cardiovascular disease and diabetic nephropathy (DN), contribute to a heavy burden on the social-economic health-care system. Baseline BCAA and aromatic amino acids (tyrosine and phenylalanine) have been shown to have significant associations with future diabetes development in a 12-year follow-up study [5]. Newgard et al showed that metabolomics profiling obese versus lean humans demonstrated a BCAA-related metabolite signature, suggesting that increased catabolism of BCAA is correlated with insulin resistance [6]. More recent studies demonstrated that a BCAA-restriction diet may promote metabolic health and improve insulin sensitivity in both lean and obese mice [7,8,9]
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