Obesity is one of best covered, and at the same time worst covered, topic in the news. Rightly so, since nearly every person is somehow or another hyper-concerned about their weight. Do I weigh too much? Do I not weigh enough? Does my weight accurately reflect my health? What is considered a “good” weight for my size/ build/ age/ comfort/ activity level? The news stories often hurt those efforts as much as they help. Reporters are quick to jump to the next, newest research to deplore our current state (whatever state that is). They are quick to instigate us to into trying the newest weight treatment plan. Other times they leap out in order to tell us why the previous newest weight treatment plan isn’t working for us or is possibly even harmful for us. And if all of that isn’t bad enough, worrying about it and stressing about it also causes weight gain! What a circle!

The good coverage focuses on our health. There is a strong correlation between being overweight and having Type 2 diabetes, for instance. Now, that doesn’t mean that every person who is overweight has or will get diabetes. But it’s just like when a baseball pitcher throwing strikes. There’s no guarantee that every pitch will be hit for a home run, but there sure is a better chance of it if the ball is constantly over the plate! And even though we live in an age where Type 2 diabetes is treatable, we still do not know the exact reason in which some biological systems becomes diabetic whereas others do not. To further our understanding of insulin resistance, the NIH has funded over $1 billion dollars each over the last three years. Those dollars are yielding fascinating clues.

Over the last decade, some key players have begun to emerge in insulin resistance. Cytokines and growth factors, ever-present in every system of our bodies whether we know it or not, work in conjunction with insulin to regulate blood sugar and fat deposits. One critical growth factor that has generated a lot of news recently is Fibroblast Growth Factor 21 (FGF21). FGF21 is an endrocrine protein (hFGF) of the FGF family of growth factors. The hFGF family typically has low affinity for heparin-binding sites and has been found to act on target cells far from their site of production. These FGFs play a significant role as regulatory hormones in bile acid metabolism, phosphate and Vitamin D metabolism as well as postnatal energy metabolism. The hFGF family also requires the use of co-receptors, like Klotho or βKlotho in order to activate any FGFRs, indicating that they have evolved a novel mechanism of regulation unlike any of the other FGF genes.

FGF21 is primarily secreted by the liver and has been shown to play a role as an antidiabetic and antiobesity agent, activating thermogenesis in brown adipose tissue and increasing body temperature. But though FGF21 is considered to be metabolically protective, helping the body to resist obesity, fatty liver and insulin resistance, it is also found in higher levels in obese conditions and does not change with weight loss (though significant fasting leads to an increase in FGF21 levels). Recently, a group led by Dorit Somocha-Bonet, from the University of New South Wales, looked into the effect of overfeeding on several growth factors, including FGF21 and FABP4. Somocha-Bonet’s group found correlations with previous work that FGF21 increase is directly related to the increased delivery of fatty acids to the liver and also discovered that FGF21 is regulated by both feeding AND fasting signals, probably in an attempt to maintain insulin sensitivity. However, their FABP4 results contrasted with previous studies which showed that weight loss and exercise also reduced FABP4. Instead, they showed that FABP4 is not increased with overfeeding, suggesting that FABP4 production is a consequence of something later in an obese state.

There is still a lot of work that needs to be done to best understand these interactions. But piece by piece, I believe that we will crack the biological code around diabetes and learn to treat the cause instead of just the symptoms…and maybe one day throw that obese batter a curve ball.

Heilbronn LK, Campbell LV, Xu A, Samocha-Bonet D (2013) Metabolically Protective Cytokines Adiponectin and Fibroblast Growth Factor-21 Are Increased by Acute Overfeeding in Healthy Humans. PLoS ONE 8(10): e78864. doi:10.1371/journal.pone.0078864

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