Taurine Activates SIRT1/AMPK/FOXO1 Signaling Pathways to Favorably Regulate Lipid Metabolism in C57BL6 Obese Mice

Mol Nutr Food Res. 2024 Apr;68(8):e2200660. doi: 10.1002/mnfr.202200660. Epub 2024 Mar 29.

Abstract

Scope: The identification of novel therapeutic agents capable of modulating lipid metabolism holds a promising potential in combating obesity and its associated complications. This study is conducted to evaluate the lipid lowering effect of dietary taurine administration on high-fat fed C57BL6 mice and to study the mechanism by which taurine impacts lipid metabolism.

Methods and results: C57BL6 mice are grouped into four (n = 6): i) normal diet (ND), ii) a high-fat diet (HFD), iii) HFD + orlistat (STD), iv) HFD + taurine (TAU) group for 12 weeks. The results show that taurine administration for 12 weeks reduces high fat-induced weight gain, and liver weight when compared with HFD fed mice. It also improves serum biochemical parameters like total cholesterol and triglycerides. Sirtuin 1 (SIRT1) activity, Nicotinamide adenine dinucleotide (NAD+) levels, SIRT1 mRNA, and protein expression are increased in HFD + TAU diet group as compared to HFD group. Taurine treatment suppresses the expression of lipogenic genes (sterol regulatory element binding protein 1c [SREBP1c], fatty acid synthase [FAS], Peroxisome proliferator-activated receptor gamma [PPARγ]) and increases the expression of β-oxidation (peroxisome proliferator-activated receptor alpha [PPARα], liver x receptor beta [LXRβ], peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC1α], AMP-activated protein kinase [AMPK]) and lipolytic (forkhead box protein O1 [FOXO1]) genes. Further, taurine mitigates hepatic inflammation by suppressing nuclear factor kappa B (NF-κB) gene expression and pro-inflammatory cytokine markers (IL-6, IL-1β, and TNFα).

Conclusion: Taurine exerts lipid lowering effects through activating SIRT1/AMPK/FOXO1 signaling pathways and regulating their downstream targets.

Keywords: SIRT1; high fat diet fed mice; obesity; taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Forkhead Box Protein O1 / metabolism
  • Lipid Metabolism* / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity* / drug therapy
  • Obesity* / metabolism
  • Signal Transduction* / drug effects
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Taurine* / pharmacology

Substances

  • AMP-Activated Protein Kinases
  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Taurine