Fast food fans world over, you may want to rethink you dietary choices. A recent study published in Science Translational Medicine showed that eating large amounts of high calorie food can cause metabolic changes, leading to a state of insulin resistance. Insulin resistance predisposes the body to the development of type 2 diabetes.
Insulin is a hormone that helps in the absorption of blood sugar by skeletal muscles and fat tissue. Diabetes mellitus type 2 is a metabolic disorder in which the body is unable to appropriately utilize the insulin produced, leading to the accumulation of glucose in blood. To deal with the excess glucose, the body produces more insulin, leading to an impasse known as insulin resistance. Type 2 diabetes is caused by a combination of genetic and lifestyle factors and differs from Type 1 diabetes, which is an autoimmune disorder in which the body makes no insulin at all. While the link between obesity and type 2 diabetes has been previously established, the exact nature and sequence of metabolic events are yet to be characterized.
Researchers led by Dr. Guenther Boden (MD) and Dr. Salim Merali (PhD) at Temple University in Philadelphia sought to specifically identify the initial metabolic changes that lead to insulin resistance. In their study, they recruited a group of six male adults, whose weights ranged between normal and overweight, and put them on a high calorie diet.
A normal American male consumes around 2500 calories. The subjects in this study were made to consume nearly 6000 calories everyday for a week and had minimal physical activity. On analyzing urine and fat tissue samples, researchers found high levels of PGF2α, a biomarker of oxidative stress, representing an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them.
38 other proteins involved in managing oxidative stress were also found to be highly expressed in the subjects, indicating that oxidative stress could be a key early event in the development of insulin resistance. This effect was observed as early as day 2 of the high calorie diet.
Dr. Merali and his team then studied the effects of the high calorie diet on an insulin-dependent molecule called Glut4, which helps in transporting blood glucose into fat tissues. Interestingly, they found that Glut4 had undergone certain chemical changes that rendered it dysfunctional.
“Surprisingly, insulin resistance was not associated with free fatty acid, inflammatory cytokines and endoplasmic reticulum stress in adipose tissue. The oxidative stress caused a change in a protein that transports glucose (GLUT4). This is the first demonstration in humans of a direct mechanistic link between excessive nutrient intake and the development of insulin resistance. We may have found the initial events that are responsible for the insulin resistance,” said Dr. Merali in a press release.
Follow-up studies on a larger and more heterogeneous cohort confirming that the Glut4 modification is directly caused by oxidative stress would further help validate the author’s claims. It would also be interesting to know if switching to a healthy diet could reverse the metabolic changes caused by high calorie diets.
Source: Medical express
The original article can accessed here.