| Summary: | Abstract Objective Recently, a positive correlation between alanine transaminase activity and body mass was established among healthy young individuals of normal weight. Here we explore further this relationship and propose a physiological rationale for this link. Design Cross-sectional statistical analysis of adiposity across large samples of adults differing by age, diet and lifestyle. Subjects 46,684 19–20 years old Swiss male conscripts and published data on 1000 Eskimos, 518 Toronto residents and 97,000 North American Adventists. Measurements Serum concentrations of the alanine transaminase, post-prandial glucose levels, cholesterol, body height and weight, blood pressure and routine blood analysis (thrombocytes and leukocytes) for Swiss conscripts. Adiposity measures and dietary information for other groups were also obtained. Results Stepwise multiple regression after correction for random errors of physiological tests showed that 28% of the total variance in body mass is associated with ALT concentrations. This relationship remained significant when only metabolically healthy (as defined by the American Heart Association) Swiss conscripts were selected. The data indicated that high protein only or high carbohydrate only diets are associated with lower levels of obesity than a diet combining proteins and carbohydrates. Conclusion Elevated levels of alanine transaminase, and likely other transaminases, may result in overactivity of the alanine cycle that produces pyruvate from protein. When a mixed meal of protein, carbohydrate and fat is consumed, carbohydrates and fats are digested faster and metabolised to satisfy body’s energetic needs while slower digested protein is ultimately converted to malonyl CoA and stored as fat. Chronicity of this sequence is proposed to cause accumulation of somatic fat stores and thus obesity.
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