Identifying genes that play a role in human fat distribution and metabolism
MINNEAPOLIS/ST. PAUL (02/15/2023) — Published in Nature Genetics, a team of researchers from the University of Minnesota Medical School and the University of Chicago found data identifying “jumping genes” — associated with fat distribution in the abdomen — that are linked to a higher risk for health complications from obesity in women.
The team identified approximately 100 genes associated with fat deposition in women. “These genes had genetic variations in transposable elements present in apes and humans, so this sexually dimorphic adipose distribution appears late in evolution for primates,” says Dr. Ricardo Battaglino, a professor of rehabilitation medicine at the U of M Medical School and corresponding author of the study.
The researchers found one of the genes, SNX10, to be strongly associated with cholesterol and triglycerides in women, which have implications for cardiovascular health. In studies done in animal models, SNX10 was found in adipocytes, and only the females that lacked SNX10 were impervious to obesity and diet-induced fat expansion.
By identifying possible genes that regulate fat accumulation, this study underlines genes, like SNX10, and pathways that may be a therapeutic goal in highlighting metabolic complications of obesity in women.
“The involvement of primate-specific elements in body fat distribution could represent one mechanism for the rapid evolution of this trait within the human lineage. Humans have a body fat phenotype that is unique among great apes, as characterized by increased body fat, especially in women,” Dr. Battaglino said. “If primate-specific Alu elements, short repetitive sequences in the DNA like a type of ‘jumping gene’ that exist only in primates, are involved in the evolution of human-specific body fat distribution, some gene targets of Alu elements may be missed by approaches that focus on non-primate model organisms.”
The research team plans to continue their study to focus on how Alu repeats participate in gene regulation in adipocytes and shape regulatory landscapes of genes involved with metabolic traits and human diseases. They will also focus on the mechanisms that may explain the effect of SNX10 deficiency on adipose tissue formation and function.
This study was funded by the Novo Nordisk Foundation, Novo Nordisk Foundation grant, the National Institutes of Health and the American Heart Association.
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