**8. Conclusion**

450 Lipid Metabolism

**6.3. G protein-coupled receptors** 

GPR43 and TLR4 overexpression.

role in lipid metabolism.

**7. New mechanisms exploration** 

Voltan et al found that *L. crispatus* M247 could increase TLR2 mRNA level and reduced TLR4 mRNA and protein levels in the colonic mucosa, suggesting that *L. crispatus* M247

It has been well-established that probiotic bacteria exert benecial effects on the intestine especially the antimicrobial property by producing organic acids or regulating the organic acid-producing flora [93]. It has been also reported that GPR41 and GPR43 can be activated by short-chain fatty acids(SCFAs)[101]. Thus, it is possible that probiotic may affect GPRs through production of SCFAs in gut. However, this relationship among these have not yet been well-established. Study performed in Gpr41-deficient mice under germ free or conventional environment revealed that present of microflora was associated with harvest

By our knowledge, only one study has investigated the effect of prebiotic which can specifically increase intestinal probiotic bifidobacteria on GPR43 expression through modified lipid profile [103]. Using a high-fat fed rodent model, the authors studied the effects of prebiotic on changes of microflora, adipose fatty acid profile and receptors expression. High fat diet is able to increase GPR43 and TLR4 expression as well as PPAR-γ expression due to oleic acid and α-linolenic acid production, while prebiotic decreases

In the past recent years, new mechanisms of probiotics on lipid metabolism were proposed. A research by Khedara et al showed lower nitric oxide level has been responsible for hyperlipidemia since endogenous nitric oxide can reduce fatty acid oxidation [104]. Some probiotics had ability to induce nitric oxide synthesis through activation of inducible nitric oxide synthase [105] [106]. Thus, modied NO availability by probiotics play an important

Moreover, Tanida et al demonstrated that *Lactobacillus paracasei* ST11 could increase adipose tissue lipolysis through enhancing the autonomic nerve activity [107]. In liver, probiotics also exhibited lipid-reducing effects [108]. Ma et al demostrated that VSL#3 probiotics could increase hepatic NKT cell numbers to attenuate high fat diet-induced steatosis [109]. Huang et al found that *L. acidophilus* 4356 could downregulate the Niemann-Pick C1-Like 1 (NPC1L1) level in the duodenum and jejunum of high-fat fed rats [110]. Another recent study by Aronsson et al revealed a new mechanism of *Lactobacillus paracasei* F19 to reduce fat storage by up-regulating levels of Angiopoietin-Like 4 Protein (ANGPTL4) in mice [84].

Omics technology provide a new insight into the mechanisms of lipid metabolism influenced by probiotics. Lee et al demostrated that gene ccpA (encodes catabolite control protein A) had function in cholesterol reduction in vivo by comparation of cholesterolreducing strain *L. acidophilus* A4 and the BA9 mutant strain with no lipid-lowering effect

of short-chain fatty acids from the diet which control the degree of adiposity [102].

maintain the Th1 / Th2 homeostasis through TLR2 / TLR4 banlance [100].

In conclusion, probiotic is a better prevention and treatment strategy for regulating lipid homeostasis with the high prevalence of obesity, burden of amazing overweight and developing chronic diseases in the modern world. Despite the fact that people too pay attention to the thin result to neglect the drug side effect, probiotic can avoid this to achieve a healthy weight. Enhancing bile acids enflux and gut cholesterol assimilation was considered as the classic theory for cholesterol-reducing probiotics. Nevertheless, rencent studies focus on antioxidant activity and interaction with lipoprotein, hormones and the whole microbiota. Besides, crosstalk among NRs, GPRs and TLRs by probiotics is new frontiers for mechanical research. However, further investigations are needed to identify various responses related to lipid metabolism influenced by probiotics.
