Dual function of Lactobacillus kefiri DH5 in preventing high-fat-diet-induced obesity: direct reduction of cholesterol and upregulation of PPAR-α in adipose tissue

Mol Nutr Food Res. 2017 Nov;61(11). doi: 10.1002/mnfr.201700252. Epub 2017 Aug 29.

Abstract

Scope: Kefir consumption inhibits the development of obesity and non-alcoholic fatty liver disease (NALFD) in mice fed 60% high-fat diet (HFD). To identify the key contributor of this effect, we isolated lactic acid bacteria (LAB) from kefir and examined their anti-obesity properties from in vitro screening and in vivo validation.

Methods and results: Thirteen kefir LAB isolates were subjected to survivability test using artificial gastrointestinal environment and cholesterol-reducing assay. Lactobacillus kefiri DH5 showed 100% survivability in gastrointestinal environments and reduced 51.6% of cholesterol; thus, this strain was selected for in vivo experiment. Compared to the HFD-saline group, the HFD-DH5 group showed significantly lower body weight (34.68 versus 31.10 g; p < 0.001), epididymal adipose tissue weight (1.39 versus 1.05 g; p < 0.001), blood triglyceride (38.2 versus 31.0 mg/dL; p < 0.01) and LDL-cholesterol levels (19.4 versus 15.7 mg/dL; p < 0.01). In addition, L. kefiri DH5 administration significantly modulated gut microbiota of HFD-fed mice. The hepatic steatosis was significantly milder (Lesion score, 2.1 versus 1.2; p < 0.001) and adipocyte diameter was significantly smaller (65.1 versus 42.2 μm; p < 0.001) in the HFD-DH5 group. L. kefiri DH5 upregulated PPAR-α, FABP4, and CPT1 expression in the epididymal adipose tissues (2.29-, 1.77-, and 2.05-fold change, respectively), suggesting a reduction in adiposity by stimulating fatty acid oxidation.

Conclusion: L. kefiri DH5 exerts anti-obesity effects by direct reduction of cholesterol in the lumen and upregulation of PPAR-α gene in adipose tissues.

Keywords: Cholesterol reduction; High fat diet; Lactobacillus kefiri; Obesity; PPAR-α.

Publication types

  • Validation Study

MeSH terms

  • Adipose Tissue, White / enzymology
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Adiposity
  • Animals
  • Carnitine O-Palmitoyltransferase / genetics
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cholesterol, Dietary / adverse effects
  • Cholesterol, Dietary / metabolism
  • Diet, High-Fat / adverse effects
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism
  • Feces / chemistry
  • Feces / microbiology
  • Gene Expression Regulation
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / microbiology
  • Hypercholesterolemia / pathology
  • Hypercholesterolemia / prevention & control*
  • Kefir / microbiology
  • Lactobacillus / classification
  • Lactobacillus / growth & development
  • Lactobacillus / isolation & purification
  • Lactobacillus / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Microbial Viability
  • Molecular Typing
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / microbiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Obesity / metabolism
  • Obesity / microbiology
  • Obesity / pathology
  • Obesity / prevention & control*
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Probiotics / therapeutic use*
  • Random Allocation
  • Republic of Korea

Substances

  • Cholesterol, Dietary
  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • PPAR alpha
  • Carnitine O-Palmitoyltransferase