Richard White, M.D. - Research to address obesity in African-American youth



Obesity: Take the 'White' Out of Fat Cells

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PHOENIX — THURSDAY, May 2, 2013 —Precursor fat cells can be transformed into metabolically active 'brown' fat cells, potentially opening a path to new obesity therapies, researchers reported here.

In a small study, preadipocytes taken from human neck fat – one of the few main locations of brown fat in an adult human – were differentiated into metabolically active fat in vitro, Aaron Cypess, MD, PhD, of Harvard, and colleagues reported at the American Association of Clinical Endocrinologists meeting here.

Further, when stimulated, those differentiated cells expressed high levels of several hallmark brown adipose tissue genes, including UCP1, according to findings also reported online inNature Medicine.

"We showed that we could take precursor fat cells ... and we could push them to become brown fat," Cypess toldMedPage Today. "The key is that we got them to respond to the activation [technique]."

Because of their induced origin, researchers call them "beige" fat cells, or "brite" cells, for a combination of brown and white, Cypess explained.

It's long been known that white adipose tissue stores excess calories, while its brown counterpart is more metabolically active, burning excess lipids in order to help maintain the body's core temperature.

Researchers once held that brown fat was only present in animals and in human infants, but more work has shown that it also clusters in certain parts of the adult human body, including the neck and collarbone.

To more accurately characterize brown fat in adults, Cypess and colleagues took neck adipose tissue from 31 patients who were having surgery. Fat was sampled from five different spots, in order of most superficial to the deepest: subcutaneous, subplatysmal, carotid sheath, longus colli, and prevertebral.

They found that human neck fat had similar histological and gene-expression characteristics to that of rodent adipose tissue, in terms of both white and brown fat.

Superficial adipose tissue had significantly more leptin gene expression, while deeper fat had greater expression of UCP1.

Cypess said brown adipose tissue was consistently most abundant in deeper fats, particularly near the carotid sheath and longus colli muscles.

He and colleagues also set out to determine the probable developmental lineage of these cells. They found in three complementary marker analyses that deep human neck brown adipocytes closely resembled cells from the classical/constitutive brown adipose tissue lineage in mice.

"Functionally, this may indicate that human neck brown adipose tissue may have the same capacity for high rates of energy expenditure seen in rodent [brown fat]," he and colleagues wrote in the paper.

They noted that the ability to grow new functional brown fat would be crucial in order to push the potential of the therapy to treat obesity and metabolic disease.

Cypess and colleagues isolated preadipocytes from human neck adipose tissue and differentiated them in vitro into brown fat cells.

They found that when stimulated, those cells had higher levels of gene expression – particularly UCP1 and another hallmark gene PPARGC1A — resembling that of brown fat, indicating that the early cells have the "capacity to respond to adrenergic stimulation with expression of genes needed for thermogenesis and are therefore bona fide brown adipocytes."

With the creation of this cell line, "we have the tools now to study [these cells] more efficiently and rapidly," Cypess toldMedPage Today. But he cautioned that the potential of brown fat in obesity therapy is a long way from the clinic.






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Date: 12.12.2018, 18:19 / Views: 94443