Distinct utilization of biotin in and between adipose and brain during aging is associated with a lipogenic shift in Wistar rat brain

Abstract

Tissue-specific metabolism determines their functions that collectively sense and respond to numerous stress cues to achieve systemic homeostasis. Chronic stress skews such metabolic profiles and leads to failure of organs as evidenced by a bias towards lipid synthesis and storage in the aging brain, muscle, and liver under Alzheimer's disease, sarcopenia, and non-alcoholic fatty liver disease, respectively. In contrast, the tissue destined for lipid synthesis and storage, such as adipose, limits its threshold and develops diabetes mellitus. However, the underlying factors that contribute to this lipogenic shift between organs are unknown. From this perspective, differential biotin utilization between lipid-rich tissues such as adipose and brain during aging was hypothesized owing to the established role of biotin in lipogenesis. The same was tested using young and aged Wistar rats. We found that adipose-specific biotin content was much higher than the brain irrespective of aging status, as well as its associated cues. However, within tissues, the adipose fails to maintain its biotinylation levels during aging whereas the brain seizes more biotin and exhibits lipid accumulation. Furthermore, mimicking the age-related stress cues in vitro such as high glucose and endoplasmic reticulum stress deprive the astroglial biotin content, but not that of adipocytes. Lipid accumulation in the aging brain was also correlated with increased S-adenosylmethionine levels and biotin utilization by astrocytes. In summary, differential biotin utilization between adipose and brain under aging and their respective cell types like adipocytes and astrocytes under age-associated stress cues connects well with the lipogenic shift in rat brain.