Gut microbiome and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally and imposed a heavy economic burden on society and individuals.To date,the pathological process of NAFLD is not yet fully elucidated.Compelling evidences have demonstrated the pivotal role of gut microbiota in the pathogenesis of NAFLD,and gut dysbiosis has been commonly observed in patients with NAFLD.Gut dysbiosis impairs gut permeability,allowing the translocation of bacterial products such as lipopolysaccharides(LPS),short-chain fatty acids(SCFAs),and ethanol to the liver via portal blood flow.This review aimed to shed light on the underlying mechanisms by which gut microbiota influences the development and progression of NAFLD.In addition,the potential application of gut microbiome as a non-invasive diagnostic tool and a novel therapeutical target was reviewed.

BMP4 facilitates beige fat biogenesis via regulating adipose tissue macrophages

Thermogenic beige fat improves metabolism and prevents obesity.Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis,whereas the activation of Ml macrophages,which play a major role in inflammation,impedes beige adipogenesis.Thus,the identification of factors that regulate adipose tissue macrophages(ATMs)will help clarify the mechanism involved in beiging.Here,we found that one of the secreted proteins in adipose tissue,namely,BMP4,alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting Ml macrophages.Mechanistically,the BMP4-stimutated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved.Meanwhile,BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis.Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity,these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.

Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease

Background Maple syrup urine disease(MSUD)is an autosomal recessive inherited disorder that affects the degradation of branched-chain amino acids and is associated with acute and chronic brain dysfunction.This study presents 11 new patients with MSUD and describes the clinical characteristics and gene mutations reported in Chinese individuals.Methods During 2011–2018,11 pedaitric patients with MSUD from 11 Chinese families were analyzed based on clinical characteristics and mass spectrometry,with confirmation via gene sequencing.Novel mutations affecting protein function were predicted with Mutation-Taster,PolyPhen-2,CADD and SIFT software.3D models of the mutated proteins were generated by using the SWISS-MODEL online server,and the models were visualized in PyMOL.The characteristics and gene mutations in patients with MSUD were analyzed retrospectively.Results Seventeen mutations in the BCKDHA,BCKDHB and DBT genes were found,8 of which are novel:c.55C>/T,c.349C>T,c.565C>T,c.808G>A,c.859C>G,and c.1270dupC in BCKDHA;c.275-2A>G in BCKDHB;and c.1291C>T in DBT.Eight patients died.Two patients had severe mental retardation and were physically handicapped.One patient with the intermediate type had relatively good prognosis,with mild psychomotor retardation and adiposity.Four mothers underwent amniocentesis for prenatal diagnosis during their second pregnancy;two fetuses were wild type,and two were carriers of one heterozygous mutation.Conclusions Eight novel mutations were associated with MSUD in Chinese patients.Prenatal diagnosis was successfully performed by genetic analysis.Mutations in the BCKDHB gene were found in the majority of Chinese patients with MSUD.