When troublesome white fat cells are converted into desirable brown fat cells, unwanted pounds melt away. But white fat cells tend to stay as they are—and excess weight, too, remains—in the presence of inflammation. And here’s the kicker. Excess fat, particularly abdominal fat, tends to induce inflammation, thereby disabling a fat-burning mechanism just when it is needed most.
Although inflammation places a block on white-to-brown fat conversion, this block could be lifted—but first it must be identified. Fortunately, this task has been accomplished by researchers based at the University of Bonn. These researchers report that the block is the inhibition of a molecular signaling pathway that incorporates the messenger cyclic guanosine monophosphate (cGMP). Moreover, the researchers suggest that bypassing the inhibition could enhance white-to-brown fat conversion. Since brown fat cells possess an extremely high number of mitochondria, they consume more energy, accelerate the burning of fat, and favor weight loss.
Details of the scientists’ work appeared January 3 in the journal Cell Reports, in an article entitled, “Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue.” The article describes how the scientists gave mice a high-calorie diet and examined the changes in the animals' fat tissue.
While hardly any inflammation occurred in the subcutaneous fat of obese mice and cGMP signaling was largely intact, things were very different for the deeper-lying abdominal fat: through the significant weight increase, inflammation had spread and the fat-burning turbocharger cGMP largely came to a standstill.
“Metaflammation impedes cGMP signaling in visceral, but not subcutaneous, white adipose tissue (WAT),” wrote the article’s authors. “cGMP signaling dysregulation corresponds to the degree of WAT inflammation.”
This uncovered a dual problem. Abdominal fat is considered much more dangerous than subcutaneous fat because it triggers inflammation and can promote cardiovascular diseases, for instance. According to the results uncovered in the current study, this is also where cGMP, which is important for fat-burning, was largely blocked. The researchers thus asked themselves: Is it perhaps possible to remove this block?
“In our studies in mice, we have found various starting points to convert troublesome white fat cells into desirable brown fat cells,” reported the study’s senior author, Professor Alexander Pfeifer, a researcher at the University of Bonn’s Institute of Pharmacology and Toxicology.
When the University of Bonn team looked into the cGMP mechanism, they found that it was suppressed by tumor necrosis factor α (TNFα).
“TNF-α-mediated suppression of sGCβ1 is mediated via NF-κB, whereas PKG is repressed by JNK signaling,” detailed the Cell Reports paper. “Additionally, TNF-α-activated JNK signaling suppresses PPARγ [peroxisome proliferator-activated receptor gamma] and aP2 [adipocyte Protein 2]. Taken together, the intensity of obesity-induced inflammation dictates the amplitude of cGMP signaling dysregulation in white adipocytes through distinct pathways.”
Using human subcutaneous and abdominal fat samples, the scientists, in cooperation with the University Hospital Leipzig and the Karolinska Institutet Stockholm, found similar changes not only to rodents but also to humans.
Although applications for obesity treatments in humans are still a long way off, the results indicate a direction for further research. “Obviously, one possible starting point in combatting obesity could be to inhibit the inflammatory response in abdominal fat while administering cGMP-stimulating active ingredients,” noted Prof. Pfeifer.
