title: Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders and induces a gene expression switch toward fatty acid oxidation in SHR.Cg-Leprcp/NDmcr rats.
abstract: Increased energy intake and reduced physical activity can lead to obesity, diabetes and metabolic syndrome. Transcriptional modulation of metabolic networks has become a focus of current drug discovery research into the prevention and treatment of metabolic disorders associated with energy surplus and obesity. Tang-Nai-Kang (TNK), a mixture of five herbal plant extracts, has been shown to improve abnormal glucose metabolism in patients with pre-diabetes. Here, we report the metabolic phenotype of SHR.Cg-Leprcp/NDmcr (SHR/cp) rats treated with TNK. Pre-diabetic SHR/cp rats were randomly divided into control, TNK low-dose (1.67 g/kg) and TNK high-dose (3.24 g/kg) groups. After high-dose treatment for 2 weeks, the serum triglycerides and free fatty acids in SHR/cp rats were markedly reduced compared to controls. After 3 weeks of administration, the high dose of TNK significantly reduced the body weight and fat mass of SHR/cp rats without affecting food consumption. Serum fasting glucose and insulin levels in the TNK-treated groups decreased after 6 weeks of treatment. Furthermore, TNK-treated rats exhibited obvious improvements in glucose intolerance and insulin resistance. The improved glucose metabolism may be caused by the substantial reduction in serum lipids and body weight observed in SHR/cp rats starting at 3 weeks of TNK treatment. The mRNA expression of NAD+-dependent deacetylase sirtuin 1 (SIRT1) and genes related to fatty acid oxidation was markedly up-regulated in the muscle, liver and adipose tissue after TNK treatment. Furthermore, TNK promoted the deacetylation of two well-established SIRT1 targets, PPARγ coactivator 1α (PGC1α) and forkhead transcription factor 1 (FOXO1), and induced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in different tissues. These observations suggested that TNK may be an alternative treatment for pre-diabetes and metabolic syndrome by inducing a gene expression switch toward fat oxidation through the activation of SIRT1 and AMPK signaling.
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Linyi
authors: L
authors: Li
authors: School of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
authors: Hisae
authors: H
authors: Yoshitomi
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Ying
authors: Y
authors: Wei
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Lingling
authors: L
authors: Qin
authors: Dongzhimen Hospital Eastern Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors: Jingxin
authors: J
authors: Zhou
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Tunhai
authors: T
authors: Xu
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Xinli
authors: X
authors: Wu
authors: Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors: Tian
authors: T
authors: Zhou
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Wen
authors: W
authors: Sun
authors: Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors: Xiangyu
authors: X
authors: Guo
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Lili
authors: L
authors: Wu
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Haiyan
authors: H
authors: Wang
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Yan
authors: Y
authors: Zhang
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Chunna
authors: C
authors: Li
authors: Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China.
authors: Tonghua
authors: T
authors: Liu
authors: School of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
authors: Ming
authors: M
authors: Gao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000097:blood; D000818:Animals; D001835:Body Weight; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D056564:Sirtuin 1 / Q000097:blood; D014280:Triglycerides / Q000097:blood*
chemical_list: D004365:Drugs, Chinese Herbal; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose