by Manisha Kashyap, PhD
Recent research has uncovered a novel mechanism by which sympathetic neuropeptide Y (NPY) contributes to obesity prevention through its role in maintaining thermogenic fat. The study, published August 28, 2024 in Nature, demonstrates that NPY from sympathetic neurons is essential for sustaining energy expenditure and protecting against diet-induced obesity, independent of food intake. The open-access article is titled “Sympathetic Neuropeptide Y Protects from Obesity by Sustaining Thermogenic Fat.” Human mutations in the NPY gene have been previously associated with high body mass index (BMI) but without significant changes in dietary patterns. The current study, led by Ana I. Domingos, PhD, Professor of Neuroscience, and her team at the University of Oxford, and colleagues, reveals the critical function of NPY in regulating the proliferation of mural cells in both brown adipose tissue (BAT) and white adipose tissue (WAT). Mural cells are crucial as they serve as progenitors for thermogenic adipocytes, which are cells that help in burning energy and generating heat.
The researchers discovered that NPY+ sympathetic neurons predominantly innervate the vasculature of adipose tissues. These NPY-responsive cells are primarily mural cells, which are a key source of thermogenic adipocytes. Importantly, diet-induced obesity was found to cause a loss of NPY+ sympathetic axons and a corresponding depletion of mural cells, leading to impaired thermogenic function and increased susceptibility to obesity.
In animal models where NPY was selectively removed from sympathetic neurons, the loss of NPY resulted in reduced thermogenic capacity and energy expenditure. This change occurred before the onset of obesity, indicating that NPY’s role in energy balance is independent of dietary intake. Moreover, these mice developed obesity on a regular diet and were more prone to weight gain on a high-fat diet, despite no increase in food consumption.
This study highlights the contrasting roles of central and peripheral NPY in body weight regulation. While NPY in the brain has been known to stimulate appetite, peripheral NPY from sympathetic neurons appears to have the opposite effect by enhancing energy expenditure. These findings suggest potential therapeutic strategies targeting peripheral NPY pathways to combat obesity and related metabolic disorders.
Discussion
The study reveals that sympathetic neuropeptide Y (NPY) plays a vital role in regulating body weight by sustaining thermogenic fat. Mural cells, which wrap around blood vessels, serve as progenitors for thermogenic adipocytes in both brown and white adipose tissue. While NPY is known to influence appetite in the brain, its role in adipose tissue was unclear. This research clarifies that NPY in sympathetic nerves is crucial for maintaining the proliferation and function of mural cells, thereby promoting thermogenic adipocyte development and energy expenditure.
Contrary to earlier studies suggesting that NPY might promote the growth of white fat, this study shows that NPY does not directly induce adipogenesis. Instead, it sustains the population of mural cells, preventing obesity by enhancing energy expenditure. Loss of NPY in sympathetic neurons leads to a reduction in mural cells, whitening of brown fat, and increased susceptibility to obesity, even without changes in food intake. These findings highlight the opposing roles of central and peripheral NPY in body weight regulation, emphasizing the importance of energy dissipation over appetite control in maintaining metabolic health.
Conclusion
The findings underscore the importance of NPY in maintaining a healthy energy balance and protecting against obesity by sustaining the function of thermogenic fat. Understanding this mechanism opens new avenues for obesity prevention and treatment, focusing on the modulation of NPY activity in peripheral tissues.
About the Writer
Dr. Manisha Kashyap (Dr. MK)
BDS (Hons), MSc, PhD (Healthcare)
Manisha Kashyap earned a BS in Dentistry (Gold Medalist) and an MS in Clinical Research, and she is a driven PhD scholar in Health Policy and Management.
With a rich background as a Drug Safety Analyst for top-tier bio pharmaceutical companies, she blends clinical expertise with a passion for advancing healthcare accessibility and innovation through her writing career for the love of science and technology via MedKnow Research Writing Solutions.
Dr. Kashyap’s PhD thesis is on “Artificial Intelligence (AI) and Public Health: Harnessing the Power of AI for Enhanced Public Health Policy and Management.”