Qing Gan Zi Shen Tang alleviates adipose tissue dysfunction with up-regulation of SIRT1 in spontaneously hypertensive rat

Biomed Pharmacother. 2018 Sep:105:246-255. doi: 10.1016/j.biopha.2018.05.022. Epub 2018 May 31.

Abstract

Qing Gan Zi Shen Tang (QGZST) is a famous traditional Chinese medicine formula in the Jiangsu Province Hospital of Traditional Chinese Medicine for its efficacy in treating hypertension, obesity, hyperlipidemia and insulin resistance. The current study further evaluated the effects and possible mechanisms of QGZST on epididymal white adipose tissue (eWAT) dysfunction in a high-fat-diet (HFD)-fed-spontaneously hypertensive rat (SHR) model. Results showed that QGZST significantly decreased the systolic blood pressure (SBP), mean arterial blood pressure (MAP), body weights and adipocyte size of HFD-fed SHRs. Moreover, QGZST remarkably reduced the serum levels of cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting glucose, fasting insulin and HOMA-IR index, increased serum high-density lipoprotein cholesterol levels and improved glucose intolerance in HFD-fed SHRs. Furthermore, QGZST dramatically attenuated HFD-fed-induced hypersecretion of proinflammatory cytokines and hypoproduction of adiponectin in SHRs. Mechanistically, QGZST stimulated the activity of Sirtuin 1 (SIRT1) and Forkhead box protein O1 (FOXO1) and suppress the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT-enhancer-binding proteins-α(C/EBP-α), fatty acid binding protein 4 (FABP4), acetylated nuclear factor-kappa-B-p65 (acetyl-NF-кB-p65) and protein-tyrosine phosphatase 1B (PTP1B). More than that, QGZST also prevented acetyl-NF-кB-p65 nuclear accumulation. Collectively, our research demonstrated for the first time that QGZST is able to alleviate eWAT dysfunction with up-regulation of SIRT1 in HFD-fed SHRs, which might supply further insight into QGZST-mediated anti-hypertension and anti-obesity effects.

Keywords: Epididymal white adipose tissue dysfunction; Qing Gan Zi Shen Tang; SIRT1; Spontaneously hypertensive rat.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / pathology
  • Adiponectin / metabolism
  • Adipose Tissue / pathology*
  • Angiotensin II / metabolism
  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Body Weight / drug effects
  • Cell Size / drug effects
  • Chromatography, High Pressure Liquid
  • Diet, High-Fat
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Epididymis / pathology
  • Forkhead Box Protein O1 / metabolism
  • Glucose / metabolism
  • Insulin / metabolism
  • Interleukin-6 / metabolism
  • Leptin / metabolism
  • Lipids / blood
  • Male
  • Organ Size
  • PPAR gamma / metabolism
  • Rats, Inbred SHR
  • Sirtuin 1 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation* / drug effects

Substances

  • Adiponectin
  • Antihypertensive Agents
  • Drugs, Chinese Herbal
  • Forkhead Box Protein O1
  • Insulin
  • Interleukin-6
  • Leptin
  • Lipids
  • PPAR gamma
  • Tumor Necrosis Factor-alpha
  • Angiotensin II
  • Sirtuin 1
  • Glucose