Acarbose effects on energy balance, body composition, and tissues: A caloric restriction mimetic? (LB448)

A recent study has shown that administration of acarbose (ACA), an α‐glucosidase and α‐amylase inhibitor approved for use in type 2 diabetes, led to increased lifespan in mice. The mechanism for this lifespan increase is unclear; however, by reducing carbohydrate metabolism, we hypothesize that ACA acts in a manner similar to caloric restriction(definition). To test this hypothesis, a six‐month dose‐response study was performed in both male and female C57BL/6J mice treated with ACA. Groups of mice (n=9‐10) received diet with ACA at doses of 0.05% (low), 0.1% (medium), or 0.15% (high), as well as a no‐dose control. High‐dose ACA administration in male mice led to 10% lower body weight (p<0.01) and >50% smaller fat depot size (p<0.001) versus control, with similar decreases in both visceral and subcutaneous depots and no significant difference in lean mass. Total energy expenditure and activity were not different between groups, while respiratory exchange ratio tended to be lower with high‐dose ACA administration (p=0.06). In contrast to body weight, a 50% increase in food intake was observed with high‐dose ACA (p<0.001), along with a >300% increase in fecal output wet weight (p<0.001). Both small and large intestine increased >20% (p<0.001), while total filled caecum wet weight increased by >200% (p<0.001). Female mice responded similarly to males (excluding body weight differences), with a dose dependent response for multiple measures in both sexes. Similar to caloric restriction, ACA administration led to smaller fat depot size and lower body weight, though gastrointestinal changes suggest alterations to carbohydrate metabolism independent of traditional caloric restriction. Comparisons with glycemic matched diets and total caloric restriction are being further investigated. Grant Funding Source : Supported by The Ellison Medical Foundation New Scholar in Aging Award (D. Smith), UAB Neuroscience Behavioral Assessment Core (P30 NS47466), and UAB Small Animal Phenotyping Core (P30 DK056336)