Time-Restricted Feeding Induces Beiging and Rejuvenates Adipose Tissue with Beneficial Effects on Cerebral Function in Old Mice

Abstract

Adipose tissue, traditionally viewed as purely an energy reserve, has recently been unveiled as a critical endocrine organ. Through the secretion of bioactive molecules known as adipokines, adipose tissue plays a role in inter-organ communication, most notably with the brain to maintain metabolic homeostasis and cognitive function. Aberrant adipokine secretion or signaling, often exacerbated with aging, has emerged as a defining characteristic of dysfunctional adipose tissue. This dysregulation can lead to inflammatory conditions, potentially disrupting neural homeostasis and heightening the vulnerability of older individuals to cognitive impairments. This study investigated the capacity of time-restricted feeding (TRF) to promote beiging (induction of brown adipocytes positive for uncoupling protein 1(UCP1) within white adipose tissue depots) in aged mice, exploring its potential role in modulating adipokine profiles, attenuating inflammation, and mitigating age-associated cognitive decline. To test this hypothesis, we collected adipose tissue samples from 24-month-old mice that underwent 6 months of TRF and compared their profiles to both young and age-matched controls on an unrestricted (ad-lib) diet. Immunohistochemical analyses of brown adipose tissue (BAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) revealed a marked reduction in pro-inflammatory markers CD80 and F4/80hi across all adipose tissues. Notably, a shift towards an anti-inflammatory state was indicated by a pronounced increase in CD163 staining in the SAT and VAT. Additionally, the increased expression of UCP1, especially in BAT and SAT, pointed towards an enhanced thermogenic capacity, suggesting a potential metabolic advantage. This was further reinforced by an increase in electron transport chain (ETC) activity in all adipose tissues. These findings have powerful implications given the established links between systemic inflammation, disrupted adipokine signaling, and neurodegenerative conditions. The alleviated adipose inflammatory profiles measured in TRF mice not only underscore its potential metabolic benefits but also highlight its possible role in safeguarding cognitive health, especially in an aging demographic. Currently serum studies and RNA sequencing are being conducted to look at altered transcript production and to investigate the role of adipokines on the brain health of the aged TRF mice. Such insights pave the way for future research exploring dietary strategies to combat age-related cognitive decline. Stephenson Cancer Center, National Institute on Aging R03 AG070479, American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.