Caloric Restriction per se Rather Than Dietary Macronutrient Distribution Plays a Primary Role in Metabolic Health and Body Composition Improvements in Obese Mice

Abstract

Caloric restriction (CR) is of key importance in combating obesity and its associated diseases. We aimed to examine effects of dietary macronutrient distribution on weight loss and metabolic health in obese mice exposed to CR. Male C57BL/6J mice underwent diet-induced obesity for 18 weeks. Thereafter mice were exposed to a 6-week CR for up to 40% on either low-fat diet (LFD; 20, 60, 20% kcal from protein, carbohydrate, fat), low-carb diet (LCD; 20, 20, 60% kcal, respectively) or high-pro diet (HPD; 35, 35, 30% kcal, respectively) (n = 16 each). Ten mice on the obesogenic diet served as age-matched controls. Body composition was evaluated by tissue dissections. Glucose tolerance, bloods lipids and energy metabolism were measured. CR-induced weight loss was similar for LFD and LCD while HPD was associated with a greater weight loss than LCD. The diet groups did not differ from obese controls in hindlimb muscle mass, but showed a substantial decrease in body fat without differences between them. Glucose tolerance and blood total cholesterol were weight-loss dependent and mostly improved in LFD and HPD groups during CR. Blood triacylglycerol was lowered only in LCD group compared to obese controls. Thus, CR rather than macronutrient distribution in the diet plays the major role for improvements in body composition and glucose control in obese mice. Low-carbohydrate-high-fat diet more successfully reduces triacylglycerol but not cholesterol levels compared to isocaloric high-carbohydrate-low-fat weight loss diets.

Effects of Diet Macronutrient Composition on Weight Loss during Caloric Restriction and Subsequent Weight Regain during Refeeding in Aging Mice

“…Each group consisted of 22-23 animals, and received purified diets (Ref# D12451 for HF, Ref# D17100401 for HC, Ref# D17100402 for HP, respectively) produced by Research Diets Inc. (New Brunswick, NJ, USA). Additional information about the diets is presented in our previous study [11]. The amount of food provided was adjusted for the different energy densities of the diets (5.2, 4.1 and 4.3 kcal/g for HF, HC and HP, respectively) to match the total energy content in the groups.…”

“…Muscles were trimmed from all visible tendons and blotted dry before being weighed on analytical balances with a precision of 0.1 mg (ABS 80-4, Kern, Balingen, Germany). White adipose tissue (subcutaneous, gonadal, mesenteric and perirenal fats) and brown adipose tissue (intrascapular fat) were dissected to assess changes in body fat [11]. The summed weight of all fat served as a body fat index.…”

“…The aim of our current study was to investigate effects of dietary macronutrient composition on physiological adaptations of old C57BL/6 mice to 30% CR followed by a period of ad libitum feeding. Our previous study showed that weight and fat loss does not depend on macronutrient proportions of the diet in adult mice undergoing CR [11]. It is important to investigate if this is true for old mice, which show greater weight loss than adult mice when subjected to 30% CR [15].…”

“…Caloric restriction (CR) is an effective intervention for weight loss regardless of the diets or dietary macronutrient allocation followed [9][10][11]. However, weight loss and related health benefits often disappear after return to the unrestricted feeding [12].…”

Everything in moderation or moderating everything? Nutrient balancing in the context of evolution and cancer metabolism

“…And can we attribute this capacity to all organisms? For instance, 'balance' could track many things, such as getting enough nutrients or avoiding excesses, or it could be quantified through inputs and outputs in an energy equation-an old view still hotly debated (Hall et al 2012;Hall and Guo 2017;Raubenheimer and Simpson 2019;Minderis et al 2021;Ludwig et al 2021). Balance might even suggest the platitude of eating 'everything in moderation', still generally promoted by nutritionists (Sizer and Whitney 2020) and public health researchers (Mente and Yusuf 2018).…”