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Sunday, April 17, 2011

How Fatty Foods Lead to Diabetes

Findings provide further evidence of importance of choosing foods low in unhealthy saturated fats

FINALLY, new research from the University of North Carolina at Chapel Hill School of Medicine adds clarity to the connection between high saturated fat diet and type 2 diabetes.

Several decades ago scientists noticed that people with type 2 diabetes have overly active immune responses, leaving their bodies rife with inflammatory chemicals. In addition, people who acquire the disease are typically obese and are resistant to insulin, the hormone that removes sugar from the blood and stores it as energy.

But for years no one has known exactly how the connection between high levels of body fat (obesity), inflammation and insulin resistance, three factors that are known to increase type 2 diabetes risk.

The Chapel Hill study has found that saturated fatty acids ‒ but not the unsaturated type ‒ can activate immune cells to produce an inflammatory protein, called interleukin-1beta
Using mouse cell lines (in vitro) and genetically engineered (defective inflammasome pathway) and wild-type mice (in vivo), the researchers found that intake of the saturated fatty acid palmitate, activates the NLRP3-ASC inflammasome-triggering production of IL-1beta, as well as the additional inflammatory factors caspase-1 and IL-18.

The activation of the inflammasome then impairs insulin signaling in several target tissues, such as muscle and adipose fat, thus reducing glucose tolerance and insulin sensitivity. IL-1beta also affects insulin sensitivity through tumor necrosis factor-α-independent and dependent pathways. When fed with a high-fat diet, mice with a defective inflammasome pathway had better maintenance of glucose homeostasis and higher insulin sensitivity.

The Chapel Hill researchers found that induction of the inflammasome by saturated palmitate is distinguished by its use of the AMP-activated protein kinase and unc-51-like kinase-1 autophagy-signaling pathways, and the presence of mitochondrialreactive oxygen species.

"The cellular path that mediates fatty acid metabolism is also the one that causes interleukin-1beta production. Interleukin-1beta then acts on tissues and organs such as the liver, muscle and fat (adipose) to turn off their response to insulin, making them insulin resistant. As a result, activation of this pathway by fatty acid can lead to insulin resistance and type 2 diabetes symptoms,” explains senior study co-author Jenny Y. Ting, PhD, William Kenan Rand Professor in the Department of Microbiology and Immunology

In layman terms, a diet rich in saturated fat, in addition to causing weight gain, activates certain cells of the immune system, instructing them to produce a protein called interleukin-1beta. This molecule is known to cause inflammation throughout the body.

This molecular complex inside cells, called the inflammasome, plays an important role in immunity by triggering inflammation in response to a wide variety of harmful agents ranging from bacteria to asbestos. This inflammation, in turn, affects the tissue of muscles, the liver and other organs, impairing their ability to react to insulin. This characteristic is one of the hallmarks of type 2 diabetes

Ting and colleagues have found that palmitate, a fatty acid common in a high fat diet, triggers activation of the inflammasome. Palmitate-triggered inflammation is also responsible for interfering with the insulin sensitivity of liver cells ― a major feature of type 2 diabetes.

In addition to explaining a poorly understood set of processes that were known to increase type 2 diabetes risk, the findings also provide further evidence of the importance of choosing foods low in unhealthy saturated fats. The researchers found that unsaturated fats, like omega-3s, did not activate this process.

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