The Mechanism Of Transgenerational Inheritance Of Lipid Accumulation Induced By High-fat Foods

Lipid metabolism play an important role in life.Researchers reported that one-third of the world's adults have suffered the risk of obesity,and the growth rate of the obesity is still increasing.As a major risk factor to human health,obesity leads to multiple diseases including type 2 diabetes(adult-onset diabetes),cardiovascular disease(hypertension),dyslipidemia,and the certain related cancers(breast cancer,prostate cancer).In addition,the model organism of mice was found that the obese phenotype not only causes body damage,but also have transgenerational epigenetic inheritance(TEI)effects,which suggests that obesity has caused great harm to human public health.However,many questions remain as to how lipid accumulation leads to signals that are transmitted across generations.In this study,we established a model of Caenorhabditis elegans(C.elegans)fed with a high fat diet(HFD)that led to obvious lipid accumulation,reveal the mechanism of transgenerational inheritance of lipid accumulation by HFD.C.elegans is ideal model for study of metabolism mechanisms.In a study of C.elegans,it was also found that information from parents who experienced acute periods of starvation can be passed on to their progeny.In addition,the lipid metabolic signaling pathways and epigenetic signals are highly conserved in C.elegans and mammals.The nematode C.elegans is a relevant and tractable model for the study of multigenerational obesogenic effects.The research results of this topic are as follows:1.High-fat foods can induce wild-type N2 lipid accumulation,and the phenotype of this lipid accumulation can be inherited across generations.2.The transcription factors DAF-16 / FOXO and SBP-1,and nuclear receptors NHR-49,NHR-80 are required for transgenerational fat accumulation.3.The transgenerational inheritance of lipid accumulation induced by HFD is mediated by delta-9 desaturases(fat-5,fat-6,fat-7).4.The epigenetic modification of histone H3K4 tri-methylation(H3K4me3)plays a central role in the TEI of lipid accumulation.5.Among these genes,daf-16 functions to execute lipid metabolism,sbp-1 works to regulate the level of H3K4me3 modification,and all of them transmit the memory of lipid accumulation to descendants.In summary,this study establishes that a network of lipid metabolic genes and chromatin modifications work together to achieve multigenerational obesogenic effects.