Effects of ketogenic amino acid replacement diet on insulin resistance in mice fed with high fat diet
10.3760/cma.j.issn.1000-6699.2016.05.010
- VernacularTitle:富生酮氨基酸饮食对高脂诱导的小鼠胰岛素抵抗的影响
- Author:
Ling XU
;
Hongyan MA
;
Jia LI
;
Chenlin GAO
;
Yong XU
- Publication Type:Journal Article
- Keywords:
Amino acid;
Insulin resistance;
Metabolic syndrome
- From:
Chinese Journal of Endocrinology and Metabolism
2016;32(5):399-404
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of ketogenic amino acid ( KAA) replacement diet on insulin resistance in mice fed with high fat diet(HFD) and to analyze the possible mechanism. Methods C57BL mice were fed with a control diet, HFD, and KAA-fortified HFD(HFDKAAR)from the age of 8 weeks, and 8 weeks after HFD initiation, the HFD-fed mice were divided into two groups:one group of mice were fed the same HFD, the other group were fed HFDKAAR ( HFD→HFDKAAR ) . The metabolic evaluations were performed at the end of 16 weeks. Blood glucose levels were measured at 0, 15, 30, 60, 90, and 120 min after the injection of glucose ( 1 g/kg BW intraperitoneal glucose tolerance test, ipGTT) . The insulin,β-hydroxybutyrate, and acetoacetate levels in the plasma were measured via ELISA. The insulin resistance index ( IRI) and area under curve ( AUC) were calculated. The expression of hepatic LKB1 ( liver kinase B1 ) , AMP-activated protein kinase ( AMPK ) , and mTOR ( Mammalian target of rapamycin ) protein, and mcp-1 mRNA were measured by western blot and real-time PCR respectively. Results HFD-fed group of mice displayed significantly heavier body weight,heavier intra-abdominal fat weight, and significant deterioration of glucose tolerance at the end of 16 weeks in addition to higher insulin levels( all P<0. 05), HFDKAAR-fed mice exhibited significantly ameliorated high fat diet-induced obesity and glucose intolerance compared to the HFD-fed mice, which was associated with decreased insulin levels, IRI, AUC, and mcp-1 mRNA expression (all P<0. 05). HFD suppressed hepatic LKB1 and AMPK phosphorylation expression, and increased mTOR phosphorylation levels compared to the control diet-fed mice(all P<0. 05). In contrast, treatment with the HFDKAAR diet increased LKB1and p-AMPK expression, which was associated with suppressed p-mTOR levels compared to the HFD-fed mice(all P<0. 05). Conclusion KAA may ameliorate high fat diet-induced obesity, glucose intolerance, via normalizing the hepatic LKB1-AMPK-mTOR nutritional signal passageway. KAA replacement diet seems to be a potential nutritional intervention for the treatment for patients with metabolic defects, such as obesity, glucose intolerance, as well as metabolic syndrome.
