Saturday, May 26, 2012

Depressed because you're fat? It's not just because of the way you look.

There is plenty of data that demonstrate a correlation between people who are overweight and/or obese and their level of depression. Now a recent study in mice demonstrates that those who are obese are likely not depressed just because of the way they look but that eating a high-fat diet results in changes in brain chemistry that are directly correlated to depressive behaviors. Mice chronically fed a high-fat diet exhibit enhanced depressive behavior as evidenced by numerous stress-related tests. For example depressed mice will spend much less time out in the open or walking across an elevated platform. Both in mice and humans there is a correlation between excessive intake of energy-rich foods, such as high-fat and/or high-sugar diets, and changes in the reward circuitry in the brain.

This work was recently published in the International Journal of Obesity:
http://www.nature.com/ijo/journal/vaop/ncurrent/full/ijo201248a.html

The neural circuits that underlie motivation and reward are composed of dopamine releasing neurons in regions of the midbrain called the ventral tegmental area (VTA) and the substantia nigra that innervate the limbic system, specifically the dorsal striatum and the nucleus accumbens (NAc). The limbic system is the area of the brain that supports a variety of functions including emotion, behavior, and motivation as well as others. Evidence in animal models of obesity as well as in obese humans shows reduced dopamine signaling in the striatum. In addition to its role in motivation and reward in the limbic system, dopamine is involved in the pathophysiology and the etiology of mood disorders including depression.

These results highlight the fact that chronic consumption of high-fat diets (as well as high-sugar diets) leads to negative changes in brain circuits that regulate mood. So, not only are many people who are overweight and/or obese depressed due to low self esteem, they are propagating a viscious cycle of eating and depression and eating more because of alterations in their brain chemistry. This means that it is highly likely that getting in control of ones diet and weight will result in positive benefits not only in their physical well-being but also in their mental well-being.

EAT WELL TO BE HAPPY!!!!!

Monday, May 21, 2012

Fatty Diets make ones Brain Want More Fat

Recent data published in the journal Nature Neuroscience ( http://www.nature.com/neuro/journal/v15/n5/full/nn.3079.html ) has demonstrated that when animals are fed a fatty diet new neuron growth occurs in an important area of the brain (hypothalamus) responsible for the control of feeding behavior. Adult animals fed a high-fat diet from the time of weaning had a higher level of hypothalamic neurogenesis than animals raised on normal chow. If the researchers killed the new neurons by x-ray-mediated ablation the animals gained significantly less weight on the same high-fat diet. It is highly likely that in humans a similar fat diet-triggered increase in hypothalamic neurogenesis would lead to excessive weight gain and fat storage. The take home from this study is that hypothalamic neurogenesis may be a significant contributor to the overall picture of diet-induced obesity and diabetes. Remember a few of my other recent posts discussed the fact that "you are what your mother eats" indicating that mothers who eat caloric excess diets while pregnat have babies who are hard-wired (due to epigenetic changes) to want excess calorie intake and thus are extremely succeptible to obesity and diabetes. Now, if simultaneously, their brains are growing more neurons to promote continued desire for high calorie intake the battle of the bulge is vey likely a lost cause.

Fat Sensing Receptors and Obesity

Several novel G-protein coupled receptors (GPCRs) have identified in recent
years using a variety of screens or as a result of the complete sequencing of the human genome
that, subsequent to their characterization, were all shown to bind and be
activated by free fatty acids and/or lipid molecules. GPR120 was identified as a result of the human genome sequencing project and shown to be a member of the class A (rhodopsin-like) family of
GPCRs. GPR120 is specifically activated by long-chain non-esterified fatty acids (NEFAs) in particular in the intestines by alpha-linolenic acid (ALA) an omega-3 polyunsaturated fatty acid
(PUFA). Activation of GPR120 in the intestines results in increased glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L cells. GLP-1 is called an incretin because it induces insulin secretion from the pancreas in response to food intake (for more details on GLP-1 function visit the Gut-Brain Interactions page). GPR120 is highly expressed in adipose tissue, and proinflammatory
macrophages. The high expression level of GPR120 in mature
adipocytes and macrophages is indicative of the fact that GPR120 is likely
to play an important role in biologic functions of these cell types. In
contrast, negligible expression of GPR120 is seen in muscle,
pancreatic beta-cells (insulin secreting cells), and hepatocytes. Although not expressed at
appreciable levels in hepatocytes expression of GPR120 is highly inducible in
liver resident macrophage-like cells known as Kupffer cells. GPR120 can
be activated with a synthetic agonist (GW9508) as well as omega-3 PUFAs. For more detailed information on the mode of action of omega fat acitvation of, and signaling by, GPR120 visit the Omega Fats page. Recent studies have found that some individuals harbor loss-of-function mutations in the gene encoding GPR120 are at increased risk for obesity and insulin resistance (a hallmark of type 2 diabetes). A clinically significant mutation results in the change of an arginine residue at amino acid position 270 to histidine (R270H) in the GPR120 protein. This mutation acts as a dominant-negative meaning that it interferes with the function of the GPR120 protein synthesized from the normal gene copy. Patients with this mutation are obese, more insulin resistant, and more glucose intolerant than obese persons without the R270H mutation. Given its important role in inflammation, obesity, and insulin sensitivity, one can expect that soon there will be drugs targeting activation of GPR120 to treat obesity and diabetes.