International Business Department           Liu Bojia           August 29, 2024

  Modern society, food has become more abundant than ever, many people are no longer worried about not eating enough, more worried about is ‘eat on fat’. Today, the top academic journal ‘Nature’ published a study, pointed out that there is a hormone in the body to avoid gaining weight has a surprisingly important role. Oxford University Professor Ana Domingos led the research team found that the lack of this hormone, even if the mice do not eat much, but also easy to get fat.

  This hormone is neuropeptide Y (NPY), which is produced by the sympathetic nervous system. This is surprising because it is just the opposite of what has been known about neuropeptide Y in the past. Previous research has found that in the central nervous system, neurons in several brain regions, including the hypothalamus, release this neurohormone to stimulate appetite, drive foraging, and contribute to fat storage. However, the new study found that neuropeptide Y released by the sympathetic nervous system plays the opposite role in weight regulation as neuropeptide Y from the brain.

  To confirm how neuropeptide Y from the sympathetic nervous system regulates adipose tissue, the researchers imaged multiple areas of adipose tissue in mice. About one-third of the sympathetic neurons innervating the adipose tissue could be seen to be highly expressing neuropeptide Y, and most of them projected to the perivascular area of the adipose tissue.

  Subsequent single-cell sequencing showed that the only cells in adipose tissue that respond to neuropeptide Y signalling are almost exclusively the mural cells of blood vessels. These mural cells are the precursors of thermogenic adipocytes in adipose tissue, which are important for the animal's thermogenic capacity and energy expenditure. Further experiments showed that the proliferation and normal development of mural cells depend on neuropeptide Y from sympathetic neurons.

  Since neuropeptide Y produced by sympathetic neurons is essential for maintaining the number of thermogenic adipocytes, when mice are deprived of these hormones, the brown adipose tissue, which produces heat for the body, even ‘whitens’, turning from energy-consuming fat into energy-storing fat. With the reduction of energy consumption, over time, even without intentionally eating high-fat food, it is easy to develop the so-called late-onset obesity in adulthood.

  For the experiment, the researchers constructed a batch of mice that managed to remove neuropeptide Y from the mice's sympathetic neurons while leaving neuropeptide Y intact in their brains. When they were confronted with high-fat foods, they gained weight more rapidly and gained weight more significantly than control mice with normal neuropeptide Y, even though they did not consume more food.

  It's worth noting that genetic manipulation isn't the only thing that causes sympathetic neurons to reduce neuropeptide Y release; diet-induced obesity also damages sympathetic neurons that express neuropeptide Y in adipose tissue. The researchers compared mice on a normal diet with those on a high-fat diet and found that high-fat diet-induced obesity causes sympathetic neuropathy, which causes atrophy and degeneration of neuronal axons, resulting in less innervation and lower local concentrations of neuropeptide Y in adipose tissue.

  Taking these results together, the paper concludes that peripheral neuropeptide Y produced by sympathetic neurons can play a role in preventing obesity by maintaining the proliferation of thermogenic adipocyte progenitors. As obesity is becoming a worldwide health problem, this finding has important implications for the prevention and treatment of obesity.