April 3, 2014
Rachel A. Brewer, research assistant and doctoral candidate in the Graduate Biomedical Sciences—under the mentorship of Daniel L. Smith, Jr., PhD, assistant professor in the Department of Nutrition Sciences—was recently selected as one of ten winners in the American Society for Nutrition (ASN) Energy and Macronutrient Metabolism Research Interest Section (EMM-RIS) Student/Postdoc Abstract Competition for “Acarbose Effects on Energy Balance, Body Composition, and Tissues: A Caloric Restriction Mimetic?” She will present her abstract at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014, to be held April 26-30 in San Diego.
Recent work 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 and circulating glucose levels, Brewer and fellow researchers hypothesized that ACA may act in a manner similar to caloric restriction.
To test this hypothesis, a six-month dose-response study was performed in both male and female C57BL/6J mice—the most widely used inbred strain and the first to have its genome sequenced—treated with ACA. Groups of mice received a healthful diet with ACA at doses of 0.05 percent, 0.1 percent, or 0.15 percent, as well as a no-dose control (e.g. 0.1 percent ACA = 1g ACA/kg food). The highest dose of ACA administration in male mice led to 10 percent lower body weight and more than 50 percent smaller fat depot size versus the control, with similar decreases in both visceral and subcutaneous fat depots, while maintaining lean mass. Total energy expenditure and activity were not different between the groups, while carbohydrate metabolism tended to be lower with high-dose ACA administration.
In contrast to traditional caloric restriction, where food rations are reduced 30 to 40 percent below voluntary choice feeding, a 50 percent increase in food intake was observed with the highest dose ACA, along with a greater than 300 percent increase in fecal output. Both small and large intestine increased greater than 20 percent, while total filled caecum wet weight increased by more than 200 percent, reflecting the ACA mechanism of reduced carbohydrate digestion and absorption. Female mice responded similarly to males (excluding body weight differences), with a dose dependent response for multiple measures in both sexes.
Brewer found that, similar to caloric restriction, ACA administration led to smaller fat depot size and lower body weight, although significantly increased food intake and gastrointestinal changes suggest alterations to carbohydrate metabolism independent of traditional caloric restriction. Comparisons with glycemic matched diets and traditional caloric restriction are being further investigated.