Isoleucine Prevents the Accumulation of Tissue Triglycerides and Upregulates the Expression of PPARα and Uncoupling Protein in Diet-Induced Obese Mice

Abstract

In this study, we investigated the effects of the branched-chain amino acid l-isoleucine (Ile) on both obesity and glucose/fat homeostasis in mice that were fed a high-fat (45% energy) diet. The mice were divided into different treatment groups and given a high-fat diet for 6 wk. During the last 4 wk, Ile was dissolved and added to the drinking water to a final concentration of 2.5%. The control mice received vehicle alone. The mice in the Ile group had an almost 6% lower body weight gain and 49% less epididymal white adipose tissue (WAT) mass with the control group (P < 0.05). The hepatic and skeletal muscle triglyceride (TG) concentrations and degree of hyperinsulinemia in the Ile group mice were also lower than the control group by 38, 47, and 39%, respectively (P < 0.05). The WAT leptin concentration was also lower, whereas that of adiponectin was higher, in the Ile group compared with the control group (P < 0.05). The hepatic levels of protein CD36/fatty acid translocase, PPARalpha, and uncoupling protein (UCP) 2 and the levels of UCP3 in skeletal muscle were all greater in the Ile group than in the control mice (P < 0.05). These results demonstrate that the liver and muscle TG concentrations are both lowered by Ile treatment. In addition, the PPARalpha and UCP expression levels in the mouse tissues were greater in the Ile group compared with the controls. Our current data thus suggest that supplementation with Ile might be useful in the treatment of metabolic syndrome.

Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT

“…It has been shown that isoleucine supplement could prevent the tissue triglycerides accumulation (Nishimura et al 2010) and balance blood glucose (Ikehara et al 2008). For example, gavage administration of isoleucine has been shown to decrease the accumulation of tissue triglyceride via increasing expression of PPARa and UCPs (Nishimura et al 2010). Moreover, oral administration of isoleucine significantly decreased the plasma glucose concentration via stimulating glucose uptake in skeletal muscle (Doi et al 2005), in addition to decrease gluconeogenesis in liver (Doi et al 2007).…”

“…It has been shown that isoleucine supplement could prevent the tissue triglycerides accumulation (Nishimura et al 2010) and balance blood glucose (Ikehara et al 2008). For example, gavage administration of isoleucine has been shown to decrease the accumulation of tissue triglyceride via increasing expression of PPARa and UCPs (Nishimura et al 2010).…”

“…The effect of increasing dietary BCAAs content, however, is controversial. Some studies show that increased BCAAs prevent high-fat diet-induced obesity (Zhang et al 2007;Nishimura et al 2010), whereas others report that it either has no effect or leads to insulin resistance (Nairizi et al 2009). …”

Tissue-specific and Nutrient Regulation of the Branched-chain α-Keto Acid Dehydrogenase Phosphatase, Protein Phosphatase 2Cm (PP2Cm)

“…Leucine, isoleucine, and valine are collectively referred as branched-chain amino acids (BCAAs) 4 because they share a structural feature with a branched-side chain and common initiation steps of catabolism. BCAAs have a critical function not only as common amino acid ingredients for protein synthesis but also as potent nutrient signals to regulate mammalian target of rapamycin signaling for cell growth (1), autophagy (2), glucose utilization (3), lipid metabolism (4), neurotransmitter synthesis (5), as well as skeletal muscle growth/atrophy (6), among many others.…”

The anti-obesogenic effects of nitric oxide.

“…Feeding leucine prevented obesity in rodents 459,460 , and was associated with lower adiposity in humans 461 , while isoleucine decreased tissue TG accumulation and adiposity and increased expression of PPAR and UCPs in diet-induce obese mice 462 . Additionally, increasing BCAA levels by deletion of BCATm, the enzyme that catalyzes the first step in BCAA metabolism, completely prevents HFD-induced insulin resistance and adiposity in mice 311 .…”