Abstract
De novo lipogenesis (DNL) is a metabolic process by which carbohydrates are converted into fatty acids and used for immediate energy or stored as triglycerides for later use. Increased DNL in brown adipose tissue (BAT) is believed to be a marker of metabolic health, but indicates poor metabolism if upregulated in hepatic tissue. ChREBP is a primary regulator of whole-body DNL and promotes production of key enzymes including fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase. ChREBP is highly expressed in primary sites of lipogenesis such as the liver, intestines, and adipose tissue. In the liver, ChREBP is associated with aging-related symptoms such as increased insulin resistance and gluconeogenesis. In BAT, ChREBP plays an important role as a regulator of uncoupling protein 1 (UCP1) and DNL. Previous research has linked increased metabolic activity in BAT to increased longevity, but the effects of ChREBP-regulated DNL on aging have not been studied yet. To elucidate this relationship, we analyzed the expression of key enzymes and regulators associated with DNL in the liver and BAT of long-lived mutant mice (Ames, Snell, GHR-KO, Pappa-KO, and PTENOE). We observed a decrease in lipogenic enzymes (FASN and ACC1) and their regulator, ChREBP in the liver of the slow-aging mouse models and a contrasting increase in these same markers in BAT. Tissue-specific modulation of DNL is a shared trait among at least these five varieties of slow-aging mice, and may contribute to the extended longevity of these strains.