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Chronic Caloric Restriction Alters Nutrient Sensing in Skeletal Muscle in High‐Fat Diet Fed Rats
Author(s) -
HernandezSaavedra Diego,
Chen Hong,
Pan YuanXiang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.850.10
Subject(s) - weight loss , lean body mass , endocrinology , medicine , skeletal muscle , nutrient , caloric theory , weight gain , fat mass , body weight , chemistry , obesity , zoology , biology , organic chemistry
Caloric restriction (CR) is regarded as one of the most effective strategies for weight loss, decreasing chronic disease risk markers. However, the reduction on body weight induces both lean and fat mass loss, and the molecular mechanism underlying excessive loss of skeletal muscle mass remains largely unknown. We hypothesize that CR alters nutrient sensing pathways in muscle, causing phenotypical loss of muscle mass. To that end, the aim of our study was to analyze the changes in body composition after prolonged CR and the effect on nutrient sensing pathways. In our study, 5 to 6 week old male Sprague‐Dawley rats were fed a high fat diet (45% Kcal from fat) Ad libitum for 3 months. Rats were then divided into HF group Ad libitum (HF), maintenance group fed a control diet (ML, 100% energy requirement at baseline adjusted with body weight), and the caloric restriction group (CR, 25% energy reduction of baseline requirement with age adjustment). Food intake, body weight, and body composition were regularly monitored and recorded. Six months after the dietary intervention rats were sacrificed, nutrient sensing intermediates in serum were measured, and skeletal muscle samples were analyzed for gene expression. The HF group showed an increase of 30.5% in body weight, of which 83.0% is fat and 7.0% is lean mass, respectively. At the same time, ML maintained body weight gain (8.4%). A negative balance was observed in the CR group, with a marked 16.9% decrease in body weight, and a significant fat and lean mass reduction of 61.0% and 12.4%, respectively at the end of the experiment. Gene expression analysis of skeletal muscle revealed a 2.2‐fold increase in the expression of Activating Transcription Factor 4 ( Atf4 ) in CR group compared to HF, as well as a 3.1‐fold upregulation of proteosomal degradation factor Muscle‐Specific Ring Finger Protein 1 ( Murf1 ) and a 2.3‐fold increase in master myogenic regulator Follistatin ( Fst ). Nutrient sensing during the caloric restriction is further characterized by investigation of regulatory mechanisms of these pathways. Overall, chronic caloric restriction resulted in the activation of nutrient sensing and protein degradation pathways, which correlates to the reduced fat mass and concomitant lean mass loss in response to the reduced energy.