Researchers at Kobe University have discovered a key reason why some people lose weight more slowly than others after workouts. By studying mice that lack certain signal molecules crucial for responding to short-term exercise and regulating energy metabolism, the team has uncovered important insights that could pave the way for treating obesity.
While it is widely known that exercise helps burn fat, the efficiency of this process can vary significantly among individuals. This complexity challenges the simplistic notion of weight loss being solely about “calories in minus calories out.” Scientists have previously identified a protein called “PGC-1⍺” that appears to play a role in linking exercise with its effects on the body. However, the impact of increased levels of this protein was inconclusive in previous experiments. Recently, researchers led by Kobe University endocrinologist OGAWA Wataru have uncovered new versions of this protein – labeled as “b” and “c” – that are produced at much higher levels in muscles during exercise compared to the original “a” version.
To delve deeper, the team developed mice lacking the b and c versions of the PGC-1⍺ protein while retaining the standard a version. They monitored these mice’s muscle growth, fat burning, and oxygen consumption during rest, short-term, and long-term exercise. Human participants, including those with type 2 diabetes known to have lower levels of this signal molecule, underwent similar tests to validate the findings in mice.
Published in the journal Molecular Metabolism, the study revealed that while all versions of the signal molecule trigger similar biological responses, their differential production levels have significant health implications. The absence of the b and c versions results in a reduced ability to respond to short-term activity, leading to lower oxygen consumption and decreased fat burning during and after workouts. In humans, higher production of the b and c versions was linked to increased oxygen consumption and lower body fat percentage, highlighting the influence of skeletal muscle genes on obesity susceptibility.
Moreover, the study found that ongoing exercise boosts the production of the standard a version of PGC-1⍺, with mice showing increased muscle mass after six weeks of regular exercise regardless of whether they could produce the alternative versions of the signal molecule.
Besides muscle production, the researchers also explored changes in the different versions of PGC-1⍺ in fat tissues, but found no significant impact following exercise. However, investigations into fat burning for temperature regulation demonstrated that exposure to cold led to increased production of the b and c versions in brown adipose tissue. Mice lacking these versions experienced a drop in body temperature, suggesting a role in metabolic adjustments to short-term stimuli.
Ogawa and the team suggest that understanding the activities of the various PGC-1⍺ versions could open avenues for obesity treatment. By potentially developing drugs that increase the production of the b and c versions to enhance energy expenditure, researchers aim to address obesity without solely relying on dietary restrictions. Future research will focus on unraveling the mechanisms behind the heightened production of these signal molecule versions during exercise.
