Aging and obesity are risk factors linked to the impairment of both energy and glucose homeostasis. Conversely, reducing caloric intake or the intake of select macronutrients or amino acids, including dietary protein restriction (DPR) and methionine restriction, defends against the detrimental effects of aging and obesity. Our data demonstrate that DPR increases energy expenditure and improves glucose homeostasis, and that the metabolic hormone FGF-21 coordinates these adaptive responses to protein restriction in young mice. However, the role of FGF-21 in mediating the effects of DPR during aging remains unclear. C57BL6 mice were fed either a normal protein (NP) or a low protein diet (LP), beginning at either young (3-months) or middle (12-months) age. A separate group of middle-aged mice were fed either a high-fat (HFD) diet or a high-fat, low-protein (HFLP) diet. Bodyweight and food intake were assessed weekly in all groups. Energy expenditure and glucose tolerance were assessed at 12 and 20 months of age in young mice and 16 months of age in middle aged-mice. Serum collected at sacrifice was used to measure FGF-21 levels. LP diet increased energy expenditure and food intake, and reduced body weight gain, in both young and middle-aged mice (P<0.05), and HFLP-diet similarly reduced body weight gain relative to HFD-fed controls (P<0.05). Glucose tolerance was improved in LP-fed young mice, and in LP and HFLP fed middle-aged mice (P<0.05). Lastly, FGF-21 levels were increased in both young and middle-aged mice in response to LP-diet (P<0.05), and in response to HFLP in middle-aged mice (P<0.05). These data indicate that the interaction of age or diet-induced obesity does not blunt the effects of DPR to induce-FGF-21, reduce body weight gain, increase energy expenditure, or improve glucose homeostasis.


C.M. Hill: None. D. McDougal: None. C. Morrison: None.


National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105032, F32DK115137); Pennington Biomedical/Louisiana Nutrition Obesity Center (P30DK072476)

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