Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice

Biomed Pharmacother. 2021 Aug:140:111714. doi: 10.1016/j.biopha.2021.111714. Epub 2021 May 19.

Abstract

Aims: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism.

Main methods: Female obese, type 2 diabetic KK-Ay mice were fed diets supplemented with 0.3% or 0.8% GRO (w/w) for 4-12 weeks. Mice were euthanized and autopsied at 20 weeks old. The effects of GRO on lipid and glucose metabolism were evaluated by measuring physiological and biochemical markers using mRNA sequencing, quantitative reverse-transcription PCR, and western blot analyses.

Key findings: Compared to mice fed the control diet, GRO-supplemented mice had reduced body and white adipose tissue weights, serum levels of triglycerides and cholesterol, and improved glucose tolerance, while food intake was not affected. We found remarkable reductions in the gene expression levels of stearoyl-coenzyme A desaturase 1 (Scd1) and pyruvate dehydrogenase kinase isoenzyme 4 (Pdk4) in the liver, in addition to decreased expression of fatty acid synthase (Fasn) in inguinal white adipose tissue (iWAT). These results suggest that GRO supplementation improves lipid profiles via reduced de novo lipogenesis in the liver and white adipose tissue. Glucose metabolism may also be improved by increased glycolysis in the liver.

Significance: Our analysis of long-term supplementation of GRO in obese and diabetic mice should provide novel insight into preventing insulin resistance and metabolic syndromes.

Keywords: Glabridin; KK-A(y) mice; Licorice flavonoid; Lipid metabolism; Stearoyl-coenzyme A desaturase 1.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Dietary Supplements
  • Fatty Acid Synthase, Type I / genetics
  • Female
  • Gene Expression / drug effects
  • Glucose / metabolism
  • Glycyrrhiza*
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Obesity / diet therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Plant Extracts
  • Plant Oils / pharmacology
  • Plant Oils / therapeutic use*
  • Plant Roots
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase / genetics
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism

Substances

  • Pdk4 protein, mouse
  • Plant Extracts
  • Plant Oils
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase
  • Fasn protein, mouse
  • Fatty Acid Synthase, Type I
  • Glucose