title: Diet-induced obesity alters protein synthesis: tissue-specific effects in fasted versus fed mice.
abstract: The influence of obesity on protein dynamics is not clearly understood. We have designed experiments to test the hypothesis that obesity impairs the stimulation of tissue-specific protein synthesis after nutrient ingestion. C57BL/6J mice were randomized into 2 groups: group 1 (control, n = 16) was fed a low-fat, high-carbohydrate diet, whereas group 2 (experimental, n = 16) was fed a high-fat, low-carbohydrate diet ad libitum for 9 weeks. On the experiment day, all mice were fasted for 6 hours and given an intraperitoneal injection of (2)H(2)O. They were then randomized into 2 subgroups and either given a sham saline gavage or a liquid-meal challenge. Rates of protein synthesis were determined via the incorporation of [(2)H]alanine (5 hours postchallenge) into total gastrocnemius muscle protein, total liver protein, and plasma albumin. High-fat feeding led to an increase in total body fat (P < .001) and epididymal fat pad weights (P < .001) and elevated fasting plasma glucose levels (P < .01). Diet-induced obesity (a) did not affect basal rates of skeletal muscle protein synthesis, but did impair the activation of skeletal muscle protein synthesis in response to nutrient ingestion (P < .05), and (b) slightly reduced basal rates of synthesis of total hepatic proteins and plasma albumin (P = .10), but did not affect the synthesis of either in response to the meal challenge. In conclusion, there are alterations in tissue-specific protein metabolism in the C57BL/6J mouse model of diet-induced obesity. This model may prove to be helpful in future studies that explore the mechanisms that account for altered protein dynamics in obesity.
authors.affiliation: Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Anderson
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Gilge
authors.forename: Alison L
authors.initials: AL
authors.lastname: Steiber
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Previs
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D017666:Deuterium Oxide; D004032:Diet / Q000009:adverse effects*; D004435:Eating / Q000502:physiology*; D005215:Fasting / Q000378:metabolism*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012709:Serum Albumin / Q000096:biosynthesis
chemical_list: D009124:Muscle Proteins; D011506:Proteins; D012709:Serum Albumin; D007930:Leucine; D017666:Deuterium Oxide