5 years ago

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

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
Kun-Ho Seo, Il-Byeong Kang, Dana Jeong, Kwang-Young Song, Hyunsook Kim, Dong-Hyeon Kim
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. The proposed dual mechanism underlying the anti-obesity and anti-non-alcoholic fatty liver disease (NAFLD) effects of L. kefiri DH5 in high-fat diet (HFD)-fed mice was explored. A large proportion of the orally administered L. kefiri DH5 remains active and viable in the gastrointestinal tract and exerts potent anti-obesity effects in HFD-fed mice via a dual mechanism: (i) direct reduction of excessive cholesterol in the lumen to decrease overall fat influx, and (ii) upregulation of genes encoding PPAR-α, CPT1, and FABP4 in adipose tissue to increase fatty acid oxidation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201700252

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