Japanese researchers investigating why some people lose more weight than others during regular physical activity found those who lose weight slower may be lacking variants of a specific protein.
Scientists believe this finding ‘may open the doors for an entirely new class of weight-loss medications’, noted medicalnewstoday.com.
The researchers at Kobe University reported people who lose weight slower during regular physical activity may be lacking variants of the protein ‘PPARGC1A’, which helps regulate the body’s metabolism and response to short-term exercise.
For the study, reported in the journal Molecular Metabolism, researchers used both mouse and human models to look deeper into how the protein PGC-1α impacts exercise and its effects on the body.
Lead author Professor Wataru Ogawa explained: ‘PGC-1α is a protein that enhances expression of genes related to mitochondria, genes involved in fatty acid oxidation, and genes involved in thermogenesis, promoting efficient energy consumption in muscles.
‘When you exercise, the expression of PGC-1α in skeletal muscle increases, which in turn induces the expression of genes that promote efficient energy consumption. This is the mechanism by which energy is efficiently expended in muscles during exercise.’
Previous Japanese research identified not only the normal ‘a’ version of the PGC-1α protein, but also ‘b’ and ‘c’ versions that are slightly different. Professor Ogawa noted: ‘These new PGC-1alpha versions have almost the same function as the conventional ‘a’ version, but are produced in muscles over tenfold more during exercise, while the ‘a’ version does not show such an increase.’
Using both a mouse model and human test subjects, Ogawa’s team found not having ‘b’ and ‘c’ versions meant short-term activity had no impact on the body, causing less
fat burn during and after a workout. However, when human test subjects had both ‘b’ and ‘c’ versions, they consumed more oxygen and had a smaller percentage of body fat than those who did not; this was seen in humans who were both healthy and with type 2 diabetes.
‘Mice lacking only PGC-1alpha ‘b’ and ‘c’ not only exhibited reduced energy expenditure during exercise, but also gained weight even when housed under normal conditions,’ Professor Ogawa said. ‘The amount of food the mice consumed was not different from that of the control mice.
‘We were surprised to find this strong phenotype; these mice became obese. While there are many model mice that become obese due to increased food intake, there are few model mice that gain weight due to reduced energy expenditure.
‘Additionally, there are mouse models that gain weight when fed a high-fat diet or other special diets, but a mouse model that gains weight simply by eating a normal diet is rare. Our observations clearly support the hypothesis ‘the efficiency of energy expenditure in muscles determines the tendency to gain weight’.’
He summed up: ‘A drug that increases expression of PGC- 1alpha ‘b/c’, unlike such appetite- suppressing medications, would promote weight loss regardless of diet. This represents an entirely new class of medication.’
