Abstract
Obesity is a major public health concern and it is essential to identify effective treatments and preventative strategies to stop continued increases in obesity rates. The potential functional roles of the branched chain amino acid leucine make this amino acid an attractive candidate for the treatment and/or prevention of obesity. The objective of this study was to determine if long-term leucine supplementation could prevent the development of obesity and reduce the risk factors for chronic disease in rats fed a high-fat (60 % fat) diet. Male Sprague-Dawley rats (n = 30 per dietary treatment) were meal-fed (3 meals/day) either a control, low-fat diet (LF), control + leucine (LFL), high-fat (HF), or high-fat + leucine (HFL) for 42 days. On day 42, rats were sacrificed at 0, 30, or 90 min postprandial. Animals fed the HF and HFL diets had higher (P < 0.05) final body weights and weight gain compared to animals fed the LF and LFL diets. Leucine supplementation increased epididymal fat mass (P < 0.05) and decreased muscle mass (P < 0.05). There was no effect of leucine supplementation on postprandial glucose or insulin response. However, there was a significant effect (P < 0.05) of diet and time on free fatty acid concentrations. There was no effect of leucine on muscle markers of protein synthesis (4E-BP1, p70S6K) or energy metabolism (Akt, AMPK). Leucine supplementation decreased (P < 0.05) PGC1α expression and increased (P < 0.05) PPARγ expression in skeletal muscle. In conclusion, long-term leucine supplementation does not prevent weight gain, improve body composition, or improve glycemic control in rats fed a high-fat diet.
Keywords:
Amino acids; Body composition; Glycemic response; Leucine; Obesity; Skeletal muscle.
MeSH terms
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Adipose Tissue / drug effects
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Adipose Tissue / metabolism
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Animals
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Biomarkers / metabolism
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Blood Glucose / metabolism*
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Body Composition / drug effects
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Diet, High-Fat / adverse effects
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Dietary Fats / administration & dosage*
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Dietary Supplements*
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Energy Metabolism / drug effects
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Fatty Acids, Nonesterified / metabolism
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Gene Expression
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Insulin / metabolism
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Intracellular Signaling Peptides and Proteins
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Leucine / administration & dosage*
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Male
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Obesity / diet therapy
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Obesity / genetics
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Obesity / metabolism*
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Obesity / pathology
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PPAR gamma / agonists
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / antagonists & inhibitors
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Protein Biosynthesis / drug effects
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Rats, Sprague-Dawley
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Ribosomal Protein S6 Kinases, 70-kDa / genetics
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism
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Treatment Failure
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Weight Gain / drug effects*
Substances
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Biomarkers
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Blood Glucose
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Carrier Proteins
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Dietary Fats
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Eif4ebp1 protein, rat
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Fatty Acids, Nonesterified
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Insulin
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Intracellular Signaling Peptides and Proteins
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PPAR gamma
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Phosphoproteins
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Ppargc1a protein, rat
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases, 70-kDa
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AMP-Activated Protein Kinases
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Leucine