02\10\2011 - Relocating fat to treat obesity, diabetes

Relocating fat to treat obesity, diabetes:

An Indo-Australian research team has found a novel way to deal with the modern metabolic disorders obesity and type 2 diabetes. They have transplanted body fat tissues of rats to chest and thigh regions thereby increasing the activity of fat tissue-secreted proteins and in turn better glucose-insulin metabolism.

"This demonstrates that local factors can directly influence the fate of transplanted tissues," lead researcher Anandwardhan Hardikar told Nature India. "This is also important to understand the potential outcome of body sculpturing surgeries as well as effects of transplanting other cell types to a different site in the body," he adds.

Body fat can predict metabolic abnormalities. The high prevalence of cardiovascular disease and type 2 diabetes in South Asians and Indians has been linked to accumulation of body (visceral) fat. Adipose tissue, the main constituent of visceral fat is known to secrete a class of proteins called adipokines (adiponectin, leptin, resistin and visfatin), which play an important role in the outcome of metabolic diseases such as obesity and type 2 diabetes.

Visceral fat is functionally distinct from the subcutaneous fat depots in chest and thigh. A recent study on obese women showed that women with a healthy metabolic profile had significantly lesser body fat volume and lower insulin resistance than women with metabolic abnormalities.

Surgical removal of visceral fat was proposed as a way forward in cutting down its bad effects on metabolism. However, this does not provide metabolic advantages, possibly because visceral fat is highly mobilized. Although researchers had earlier tried fat transplantation involving donor and recipient mice, no one had tried fat transplantation from visceral to subcutaneous regions in the same mice.

Hardikar and co-researchers raised rats on high fat diets and found that the expression of adipokines in their visceral fat was 10,000 to a million-fold lower than that observed in subcutaneous (thigh or chest) regions. This prompted them to analyse the fate of autologous transplanted visceral fat in peripheral (subcutaneous) sites.

They surgically removed around 40% of visceral fat and implanted it in the thigh and chest regions. They sacrificed the animals on day 4, 21 and 30 and analysed the transplanted fat tissues.

"Post-transplant, the glucose infusion rates in the animals was more than doubled confirming that the subcutaneous fat transplant improved their glucose utilization," says Hardikar. Compared to peripheral sites such as thigh and chest, glucose is present in high concentrations in the gut region. So the researchers probee if glucose played a role in the expression of genes that code for adipokines proteins, which in turn regulate glucose-insulin metabolism.

They found that exposure to lower glucose concentration induced 200 to 2000-fold increase in expression of adipokine genes. Subcutaneous fat tissue biopsy slices cultured in high glucose concentrations demonstrated a 400- to 1500-fold suppression in gene expression. This proved why the subcutaneous niche with its characteristic low glucose level helps higher expression of adipokine genes and their products in the fat grafted in thigh or chest regions.

"This is an excellent work which shows the role of glucose in regulating adipokine genes," says Biplab Giri of Kolkata-based West Bengal State University who studies metabolic disorders.

"Though such metabolic advantage may be useful to treat type 2 diabetic patients, the study recorded a few weeks of metabolic advantage in animal model after fat transplantation. Once the visceral fat is mobilized back, it might show the same insulin resistance again," Giri adds.

Hardikar clarifies saying visceral fat is highly mobilized and recurrence of insulin resistance would depend on several factors affecting diet and lifestyle changes. "We plan to initiate specific studies addressing the long-term effects of surgical translocation of visceral adipose tissue under different dietary conditions," he says.

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