Data from: Tang-Nai-Kang alleviates pre-diabetes and metabolic disorders by inducing a gene expression switch toward fatty acid oxidation in SHR.Cg-Leprcp ⁄NDmcr rats

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.