Sex and genetic background define the metabolic, physiologic, and molecular response to protein restriction.

Low-protein diets promote metabolic health in humans and rodents. Despite evidence that sex and genetic background are key factors in the response to diet, most protein intake studies examine only a single strain and sex of mice. Using multiple strains and both sexes of mice, we find that improvements in metabolic health in response to reduced dietary protein strongly depend on sex and strain. While some phenotypes were conserved across strains and sexes, including increased glucose tolerance and energy expenditure, we observed high variability in adiposity, insulin sensitivity, and circulating hormones. Using a multi-omics approach, we identified mega-clusters of differentially expressed hepatic genes, metabolites, and lipids associated with each phenotype, providing molecular insight into the differential response to protein restriction. Our results highlight the importance of sex and genetic background in the response to dietary protein level, and the potential importance of a personalized medicine approach to dietary interventions.

Aging adipose: Depot location dictates age-associated expansion and dysfunction.

Adipose tissue has a variety of diverse functions that maintain energy homeostasis. In conditions of excess energy availability, adipose tissue increases its lipid storage and communicates the nutritional abundance to various organs in the body. In conditions of energy depletion, such as fasting, cold exposure, or prolonged exercise, triglycerides stored in adipose tissue are released as free fatty acids to support the shift to catabolic metabolism. These diverse functions of storage, communication, and energy homeostasis are shared between numerous adipose depots including subcutaneous, visceral, brown, beige, intramuscular, marrow, and dermal adipose tissue. As organisms age, the cellular composition of these depots shifts to facilitate increased inflammatory cell infiltration, decreased vasculature, and increased adipocyte quantity and lipid droplet size. The purpose of this review is to give a comprehensive overview of the molecular and cellular changes that occur in various aged adipose depots and discuss their impact on physiology. The molecular signature of aged adipose leads to higher prevalence of metabolic disease in aged populations including type 2 diabetes, cardiovascular disease, Alzheimer's disease, and certain types of cancer.