As the obesity epidemic continues to grow in the U.S., scientists are scrambling to find ways to curb the parallel rise of heart disease and diabetes. When it comes to obesity treatment, however, the only ways you can really lose weight is through exercise, eating well, some weight medications, or bariatric surgery.
A new study out of Yale, however, has found that preventing obesity and diabetes could lie in the process of keeping a nuclear receptor from being activated in the brain. The study, published in The Journal of Clinical Investigation, found that blocking a nuclear receptor called PPARgamma in some brain cells in mice resulted in the animals eating less and thus not gaining weight. The mice became somewhat resistant to a high-fat diet, the authors say.
“These animals ate fat and sugar, and did not gain weight, while their control littermates gained weight on the same diet,” said Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Science at Yale School of Medicine, in a press release. “We showed that the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity.” Nuclear receptors are a type of protein found in particular cells that are responsible for monitoring steroid and thyroid hormones. They are in charge of development, homeostasis, and metabolism of the organism.
The researchers focused on POMC neurons, which are found in the hypothalamus, and regulate food and fullness. When POMC neurons are activated, they trigger a sense of fullness and end up curbing your appetite. PPARgamma, on the other hand, regulates POMC neurons; the researchers hypothesized that if the former were blocked, it might lead to an increase in POMC neurons, which would make you feel full more often. “When we blocked PPARgamma in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active,” Diano said.
The study might also have a positive effect on diabetes research. A certain class of drugs used to treat diabetes, known as thiazolidinedione (TZD), lower blood-glucose levels but still cause patients to unfortunately gain weight. The authors found that targeting PPARgamma might be able to prevent TZD from triggering weight gain.
“Our study suggests that the increased weight gain in diabetic patients treated with TZD could be due to the effect of this drug in the brain, therefore, targeting peripheral PPARgamma to treat type 2 diabetes should be done by developing TZD compounds that can’t penetrate the brain,” Diano said. “We could keep the benefits of TZD without the side effects of weight gain. Our next step is to test this theory in diabetes mouse models.”
Before an obesity therapy is developed, however, many overweight patients might have to stick to the natural cure of exercise and diet.
Source: Diano S, Horvath T, Long L, Toda C, Jeong JK. PPARgamma ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. The Journal of Clinical Investigation. 2014.