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Is Fat Making you… Fat?


Fast food, let’s face it, it’s not the best for you. Yet Mcdonalds and Pizza hut are known practically world wide [although menu options differ]. With the rise of our waist lines and the shrinking cost of fast food, you might suspect a connection. Fortunately for your big mac addiction [no judgement] it isn’t what you might think. If you’re finding it harder and harder to see your toes, you might just have your brain, and not your stomach, to thank for it.

This is because ironically, fat is making you fat, just not in the way you think it does. The brain plays a central role in regulating appetite and in fact, whole-body metabolism. It isn’t as simple as an expanding stomach and overeating, although there is more than just a few people who would want you to think otherwise. In reality a protein known as PPARγ [Finally, I get to be fancy and use the gamma insert for my writing] is the main contributor in the brain’s control of food intake and body weight. Unfortunately, as with anything involving the brain the identity of the neurons regulating this process has been unclear.

Thankfully a study out that has demonstrates that PPARγ activity in a type of neuron known as pro-opiomelanocortin [POMC] neurons are critical in mediating the response to high-fat diet. Furthermore, when the researchers blocked the effects of the nuclear receptor PPARγ in those particular neurons  in mice, the animals ate less and became resistant to a high-fat diet.

“These animals ate fat and sugar, and did not gain weight, while their control littermates did,” said lead author Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. “We showed that the PPARγ receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity.”

POMC neurons for those who aren’t on the cutting edge of brain research, are found in the hypothalamus and specifically regulate food intake. They are the neurons that, when activated, make you feel full and help curb appetite. The researchers have shown that PPARγ regulates the activation of these neurons.

The team then studied transgenic mice that were genetically engineered to delete the PPARγ receptor from POMC neurons. They did this to see if they could prevent the obesity associated with a high-fat, high-sugar diet.

“When we blocked PPARγ in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active,” said Diano, who is also professor of comparative medicine and neurobiology at Yale and director of the Reproductive Neurosciences Group.

The findings also have important implications in the study of diabetes. PPARγ is a target of thiazolidinedione [TZD], a class of drugs used to treat type 2 diabetes. Although this drug lowers blood-glucose levels– which as I have written about before, should in turn help them lose weight — patients gain weight on these medications.

“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 PPARγ to treat type 2 diabetes should be done by developing TZD compounds that can’t penetrate the brain,” said Diano. “We could keep the benefits of TZD without the side-effects of weight gain. Our next steps in this research are to test this theory in diabetes mouse models.”

So what’s next? Could we see a new class of drugs that are PPARγ inhibitors? Well it’s possible, in the meantime it is just one more piece in the ever expanding [no pun intended] rising levels of obesity puzzle. In the short term another good piece of fat loss advice [for those in serious need], limit fat intake. Probably a no-brainer for anyone serious about losing weight, drop the big macs and start making your own chicken sandwiches, just be healthy.

But for those with diabetes or other problems [such as mental health induced eating habits, which is probably much more common than you think] this research could pave the way to help treating the problems.

Can’t wait to sink your teeth into the full study? Well you’re in luck my friend, you can find that —here!

Long L, Toda C, Jeong JK, Horvath TL, & Diano S (2014). PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding. The Journal of clinical investigation PMID: 25083994

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