Obesity and its complications are associated with chronic inflammation, but new findings show that a certain kind of inflammation is needed to prepare fat tissue for healthy weight gain. Moreover, in mice, this “good” inflammation appears to improve energy metabolism, staving off or even reversing the prediabetic phenotype. Now that this beneficial inflammatory mechanism has been identified, it may lead to new therapeutic approaches against metabolic syndrome and type 2 diabetes.
The new findings were reported by scientists led by the University of Montreal’s Przemyslaw (Mike) Sapieha, Ph.D. According to these scientists, macrophages that express neuropilin-1 (NRP1) accumulate in fat tissue and orchestrate healthy weight gain.
Details appeared March 16 in the journal Science Immunology, in an article entitled “Neuropilin-1 Expression in Adipose Tissue Macrophages Protects against Obesity and Metabolic Syndrome.” According to this article, ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages toward a more inflammatory glycolytic metabolism.
“Conditional deletion of NRP1 in LysM Cre-expressing cells leads to inadequate adipose vascularization, accelerated weight gain, and reduced insulin sensitivity even independent of weight gain,” wrote the article’s authors. “Transfer of NRP1+ hematopoietic cells improved glucose homeostasis, resulting in the reversal of a prediabetic phenotype.”
It is believed that obesity-induced metabolic syndrome is caused by excessive fat accumulation that triggers detrimental inflammation and prevents organs from functioning adequately. Consequences include poor regulation of blood sugar levels.
Depending on how many calories we take in, fat tissue expands or contracts. For fat tissue to expand in a healthy manner, it must first be prepared, much like a garden must be plowed before planting seeds. This kind of cultivation appears to be accomplished by the immune cell subset identified in the current study.
The NRP1-positive immune cells, asserts Ariel Wilson, Ph.D., the study’s lead author, are important in removing excess fat from the body. They also help build the body's infrastructure to accommodate new fat reserves without causing complications typically associated with obesity.
The study also demonstrates that transferring NPR1-positive immune cells (through the bone marrow) to mice that lack them actually helps the animals regain control of their blood sugar levels and makes the animals metabolically healthier in general.
“Our study further provides in vivo support for the notion that macrophage polarization is intrinsically associated with energy metabolism and that homeostatic macrophages rely heavily upon FAs [fatty acids] delivered via NRP1, a slower yet sustained means of energy production,” the article’s authors concluded. “More broadly, our study provides insight into the essential role of macrophages in adipose tissue homeostasis.”