Fight Aging!

In this research, scientists explore a link between the presence of excess fat and the dysfunctional blood sugar regulation that is characteristic of type 2 diabetes. The vast majority of type 2 diabetes patients suffer the condition because they are overweight, and could turn back its progression even in late stages through sustained low-calorie diets and losing that weight. Type 2 diabetes is a prevalent age-related disease because we live in an age of cheap calories and little exercise, older people have more time and opportunity to gain the necessary excess fat tissue to trigger the condition, and other mechanisms cause a decline in the aging pancreas and its beta cells, making it more likely that a given gain in weight will push metabolic syndrome over the line into full blown diabetes.

Using cells from mice and human livers, researchers demonstrated for the first time how under specific conditions, such as obesity, liver CD8+ T cells, white blood cells which play an important role in the control of viral infections, become highly activated and inflammatory, reprogramming themselves into disease-driving cells. Scientists have been trying for many years to discover why the liver continues to pump out too much glucose in people with diabetes. This paper sheds light on the markers of activation and inflammation in CD8+ T cells and the Interferon-1 pathway which helps stimulate their function. In fact, the normal function of the immune cells becomes misdirected. The pathways they would typically use to fight infection create inflammation, unleashing a chemical cascade which impacts insulin and glucose metabolism.

In the study, researchers fed mice a high-fat diet, 60 per cent of which was saturated fat, for 16 weeks. Compared with normal chow diet-fed mice, the high-fat diet mice showed worsened blood sugar, increased triglycerides, a type of fat (lipid) in the blood, and a substantial increase in the numbers of CD8+ T cells in the liver. Instead of responding to viruses or other foreign invaders in the body, the activated CD8+ T cells launch an inflammatory response to fat, and to bacterial components that migrate to the liver from the gut through the blood. The activated T-cells divide rapidly, pumping out increased numbers of cytokines, proteins that assist them in an active and excessive immune response. This pro-inflammatory response in turn interferes with normal metabolism in the liver, specifically jamming up or blocking insulin signaling to the liver cells.

Since the liver stores and manufactures glucose or sugar depending upon the body's need, the hormone insulin signals whether the liver should store or release glucose. This system keeps circulating blood sugar levels in check. If that signal is disrupted or blocked, the liver continues to make more sugar, pouring it into the bloodstream. If the liver is over-producing glucose, it becomes difficult to regulate blood sugar. "We're moving from studying diabetes as a metabolic syndrome - a combination of nutritional and hormonal imbalances - to include the role of the immune system and inflammation. That's the developing link. Inflammation is emerging to be a major mediator of insulin resistance."

The researchers found that in genetically-modified mice lacking Interferon-1, who were also fed a high-fat diet, the CD8+ T cells did not produce an inflammatory response, and the mice had near normal blood sugar levels. In further investigations of human liver cells from nearly 50 donor tissues of humans with varying degrees of body mass index (BMI) and liver fat, higher levels of CD8+ T cells were linked with higher levels of blood sugar or more advanced fatty liver disease.

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