Propionate Promotes Intestinal Lipolysis And Metabolic Benefits Via AMPK/LSD1 Pathway In Mice

Diary fiber and intestinal microbial fermentation products can supply energy to the body and promote metabolic health,but its mechanism is still unclear.Recent study showed,intestinal lipid metabolism played an important role in whole-body energy metabolism,but the way of regulation was not clear.Therefore,this study mainly explores the effects of dietary fiber and short-chain fatty acids(SCFAs)on intestinal lipid metabolism and its potential mechanism,and aims to provide an important theory for the development and rational utilization of new feed additives for improving the carcass quality of livestock and poultry.In this study,using C57/BL6J mouse as animal model,we investigated the effects of inulin and SCFAs on whole body fat mass and intestinal lipid storage by intragastric administration.Caco-2 cells were used to validate the direct role of SCFAs on intestinal enterocytes lipid metabolism and molecular mechanism.The results are as follows:(1)In chow diet,propionate and inulin could significantly reduced fat mass of mice and serum triglyceride(TG)in mice after 2 weeks treatment(P<0.05),but didn’t affected body weight gain,food intake and fecal triglyceride(P>0.05);(2)Propionate and inulin significantly decreased triglyceride in jejunum and ileum(P<0.05),and induced the mRNA expression of ATGL,HSL and LAL involved lipid lipolysis genes and fatty acid oxidation gene CPT1α(P<0.05),but did not affect intestinal triglyceride resynthesis genes DGAT1 and MGAT2 mRNA expression(P>0.05);(3)In vitro,treatment Caco-2 cells with 0.1 mM and 0.5 mM sodium propionate for 24 h significantly reduced intracellular triglyceride(P<0.05),increased the mRNA expression of ATGL,HSL and LAL,but did not affect the mRNA expression of DGAT1(P>0.05);(4)Propionate and inulin did not affect the mRNA expression of short-chain fatty acid receptors FFAR2/3 in jejunum and ileum(P>0.05),but significantly activated protein expression of p-AMPK(Th172)and histone demethylase LSD1(P<0.05);(5)Treatment Caco-2 with p-AMPK specific inhibitor Cc(10 μmol/L)for 24 h significantly blocked the increase of lipolysis genes ATGL,HSL,LAL and LSD1 by propionate(P<0.05);(6)Inhibition of LSD1 protein expression by GSK2879552(5μmol/L)for 24 h significantly reversed the increase of lipolysis genes ATGL,HSL and LAL by propionate(P<0.05),but did not affect the protein expression of p-AMPK.(7)Under high-fat diet,propionate and inulin significantly prevented high-fat diet-induced weight gain(P<0.05),and decreased body fat and serum triglyceride(P<0.05),but not effected on food intake and fecal triglyceride(P>0.05).Similar to chow diet,propionate also significantly up-regulated the mRNA expression of ATGL,HSL,LAL and CPT1α in the jejunum and ileum(P<0.05),and significantly up-regulated protein expression of p-AMPK(Thr172)and LSD1 in the jejunum and ileum when in high-fat diet(P<0.05).In conclusion,in chow diet or high-fat diet,propionate and inulin could enhance the ability of intestinal lipolysis,and reduce whole-body lipid circulation and lipid deposition.In addition,propionate,entering the intestinal epithelial cells rather than depending of short-chain fatty acid receptors FFAR2/3,activates the expression of APMK and LSD1,thus induces intestine lipolysis.