Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet.
BACKGROUND
Leucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD).


METHODS
C57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3% Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC), triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were determined.


RESULTS
Mice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase) and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, β3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue.


CONCLUSIONS
This study demonstrated that chronic leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning.
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Jun
J
Jiao
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Shu-Fen
SF
Han
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Wei
W
Zhang
School of Radiation Medicine and Protection, Soochow University, Suzhou, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
Jia-Ying
JY
Xu
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.
Xing
X
Tong
Jiangsu Bio-Engineering Research Centre of Selenium, Suzhou, China.
Xue-Bin
XB
Yin
Jiangsu Bio-Engineering Research Centre of Selenium, Suzhou, China.
Lin-Xi
LX
Yuan
Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, Suzhou, China.|Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, Soochow University, Suzhou, China; qinliqiang@suda.edu.cn.
Li-Qiang
LQ
Qin
WAT browning; brown adipose tissue; leucine; lipid metabolism; white adipose tissue