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.

Figure 1. Energy intake and growth

Male C57BL/6J mice were allowed ad libitum access to either a low-fat, high-carbohydrate diet (LF) or a high-fat, low-carbohydrate diet (HF). Energy intake (Panel A) was determined by weighing the food that remained on each cage at the end of every week and dividing by 4, i.e. the number of mice per cage. The body weight (Panel B) of individual mice was determined at the end of each week. The data are expressed as mean ± sem, n = 16 per diet group per time point (* p < 0.05).

Figure 2. Effect of diet-induced obesity on protein synthesis

Mice were maintained on either a low-fat (LF) or a high-fat (HF) diet for 9 weeks. Protein synthesis was quantified following the injection of ²H₂O via the incorporation of ²H-labeled alanine, mice were studied during either the fasted (saline gavage) or the fed (liquid meal) state. Muscle, liver and plasma albumin synthesis were quantified (Panel A, B and C, respectively). The data are expressed as the % newly made protein per hour, mean ± sem (n = 6 to 8, muscle and liver data and n = 3 to 4, albumin data), * p < 0.05 fed vs. fasted, # p < 0.05 fed vs. fed.