Adrenergic-induced remodeling of the neuro-vascular network in adipose tissue

Adrenergic-induced remodeling of the neuro-vascular network in adipose tissue

Our bodies contain two types of fat: white fat and brown fat. While white fat stores calories, brown fat burns energy and could help us lose weight. Now, scientists have found a way of making the white fat 'browner' and increasing the efficiency of brown fat.

While their study was carried out in mice, they hope that this finding will translate into humans and provide a potential new drug to help fight obesity.

Both brown and white fat are made up of fat cells known as adipocytes, but in brown fat, these cells are rich in mitochondria - the 'batteries' that power our bodies - which give the tissue its brown colour. Brown fat also contains more blood vessels to allow the body to provide it with oxygen and nutrients.

While white fat stories energy, brown fat burns it in a process known as 'thermogenesis'. When fully activated, just 100g of brown fat can burn 3,400 calories a day - significantly higher than most people's daily food intake and more than enough to fight obesity.

Just having more brown fat alone is not enough - the tissue also needs to be activated. Currently, the only ways to activate brown fat are to put people in the cold to mimic hibernation, which is both impractical and unpleasant, or to treat them with drugs known as adrenergic agonists, but these can cause heart attacks. It is also necessary to increase the number of blood vessels in the tissue to carry nutrients to the fat cells and the number of nerve cells to allow the brain to 'switch on' the tissue.

In a study published in the journal Nature Communications, an international team of researchers which has shown that increasing BMP8b in mice can increase the function of their brown fat (adipose tissue).

This implies that BMP8b, which is found in the blood, could potentially be used as a drug to increase the amount of brown fat amount in humans as well as making it more active. Further research will be necessary to demonstrate if this is the case.

To carry out their research, the team used mice that had been bred to produce higher levels of the protein in adipose tissue. As anticipated, they found that increasing BMP8b levels changed some of the white fat into brown fat, a process known as beiging and thus increased the amount of energy burnt by the tissue.

Overexpression of bmp8b in adipose tissue enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of adipose tissue were maintained at 28 °C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b.

Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity.

They showed that higher levels of BMP8b make the tissue more sensitive to adrenergic signals from nerves - the same pathway target by adrenergic agonist drugs. This may allow lower doses of these drugs to be used to activate brown fat in people, hence reducing their risk of heart attack.