In young lean men, individuals with naturally higher levels of a hormone precursor called androstenediol-sulfate tend to gain less fat and store less excess energy when consuming a high-calorie diet...
Mechanism
Synthesis from 1 study
Men who naturally have more androstenediol-sulfate in their blood before overeating burn more fat for energy in their liver and muscles, turning extra calories into heat instead of storing them as fat — this is shown in 10.1038/ijo.2013.77. Other factors like being more fit or having more active...
Most probable mechanism
Men with higher levels of androstenediol-sulfate before overeating burn more calories as heat through increased fat breakdown in muscle, liver, and fat tissue, leaving less energy available to turn into body fat — this is supported by findings from 10.1038/ijo.2013.77 that link this hormone to higher energy expenditure and lower fat gain.
Baseline plasma levels of androstenediol-sulfate are higher in individuals who gain less fat during chronic overfeeding, as directly measured in 10.1038/ijo.2013.77.
Androstenediol-sulfate promotes peroxisomal beta-oxidation in the liver and likely enhances mitochondrial fatty acid oxidation in skeletal muscle, increasing energy dissipation as heat and reducing substrate availability for lipid synthesis, as suggested by 10.1038/ijo.2013.77 and corroborated by parallel associations between oxidative enzyme activity (OGDH) and reduced fat gain in the same study.
Increased oxidation of fatty acids through mitochondrial and peroxisomal pathways reduces surplus acetyl-CoA and NADPH, limiting the raw materials needed for de novo lipogenesis, a process indirectly supported by negative correlations between oxidative capacity (OGDH activity, VO2max, TEM) and fat mass gain in 10.1038/ijo.2013.77.
The net reduction in lipid synthesis capacity results in lower fat mass accumulation despite a standardized 84,000 kcal caloric surplus, as directly observed in individuals with higher baseline androstenediol-sulfate levels in 10.1038/ijo.2013.77.
Less supported by current evidence, but not ruled out
Men with naturally higher activity of mitochondrial enzymes like OGDH in muscle burn more fat for energy during overfeeding, leaving less to be stored as fat — this is directly shown in 10.1038/ijo.2013.77.
Baseline skeletal muscle exhibits higher maximal activity of oxidative enzymes such as OGDH, directly measured in 10.1038/ijo.2013.77.
Increased OGDH activity enhances mitochondrial fatty acid oxidation and ATP synthesis efficiency, reducing the pool of acetyl-CoA available for fat synthesis, as shown by inverse correlations with fat gain in 10.1038/ijo.2013.77.
Higher oxidative flux lowers the FM-to-FFM ratio, indicating preferential energy use over storage, as demonstrated in 10.1038/ijo.2013.77.
Reduced lipid synthesis leads to lower fat mass accumulation despite identical caloric surplus, directly observed in low-FM gainers with high OGDH in 10.1038/ijo.2013.77.
Men with higher aerobic fitness (VO2max) burn more calories at rest and after meals, so more of the extra food energy is lost as heat instead of stored as fat — this is shown in 10.1038/ijo.2013.77.
Baseline VO2max per kg body mass is higher in individuals who gain less fat during overfeeding, directly measured in 10.1038/ijo.2013.77.
Higher VO2max reflects greater mitochondrial density and aerobic capacity in skeletal muscle and other tissues, increasing basal and postprandial energy expenditure, as supported by correlations with OGDH activity and reduced FM-to-FFM ratio in 10.1038/ijo.2013.77.
Increased energy dissipation through thermogenesis reduces the net energy surplus available for lipid synthesis, as shown by negative correlations between VO2max and fat mass gain in 10.1038/ijo.2013.77.
Lower fat mass accumulation occurs despite identical caloric surplus, directly observed in high-VO2max individuals in 10.1038/ijo.2013.77.
After eating, some men naturally burn more calories as heat — this thermic effect of food is higher in those who gain less fat during overfeeding, as shown in 10.1038/ijo.2013.77.
Baseline postprandial energy expenditure (TEM) is higher in individuals who gain less fat during overfeeding, directly measured in 10.1038/ijo.2013.77.
Increased postprandial thermogenesis enhances mitochondrial uncoupling and substrate oxidation in muscle, liver, and adipose tissue, reducing net energy available for storage, as inferred from negative correlations with FM-to-FFM ratio in 10.1038/ijo.2013.77.
Greater energy dissipation after meals reduces the surplus available for de novo lipogenesis, as directly observed in low-FM gainers with higher TEM in 10.1038/ijo.2013.77.
Reduced lipid synthesis leads to lower fat mass accumulation despite caloric surplus, as directly measured in 10.1038/ijo.2013.77.
Evidence from Studies
Supporting (1)
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PREDICTORS OF BODY COMPOSITION AND BODY ENERGY CHANGES IN RESPONSE TO CHRONIC OVERFEEDING
Contradicting (0)
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Gold Standard Evidence Needed
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