The research team of East China Normal University has made an important breakthrough in the field of obesity and metabolic diseases, and the team found that beige fat in humans activates thermogenesis through local hyperthermia, which can greatly reduce obesity symptoms and improve metabolic disorders. Cell magazine, the top international journal, published the results online on March 4 and selected as a cover article.
Cell cover paper design: Local hyperthermia promotes browning of white fat and improves metabolic health. The cover idea is taken from the Phenoix story (the legend of the immortal bird and the phoenix nirvana in Greek mythology). White fat undergoes Browning after hyperthermia, bursting out energy (Pheonix), bringing health to humans. The pictures in this article are all courtesy of East China Normal University
Fat is also divided into different types, including humans and mice, mammals, there are white, brown, beige three different functions of fat. White fat is responsible for storing excess heat energy, and brown fat is combustible fat that can be converted into heat. Beige fats, a newly discovered class of fats, exhibit the qualities of white fats at rest, and have the potential to brown out in cold or β adrenaline activation, which can promote thermogenesis and energy expenditure. Beige fat is distributed on both sides of the neck, on the upper back, near the collarbone, and around the spine in adults, which has the effect of sensing cold and enhancing sugar absorption and metabolism.
Ma Xinran (right) Xu Lingyan (left)
This joint study by Ma Xinran and Xu Lingyan of the Obesity and Metabolic Disease Research Group of the College of Life Sciences of East China Normal University, Professor Hu Cheng of the Metabolic Disease Genetics Research Group of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, and Zhang Qiang, a researcher of the Biomass Nanomaterials Research Group of the School of Life Sciences of East China Normal University, found that in addition to cold stimulation, beige fat can induce local mild thermal effects and activate thermogenesis through heat shock factor 1 (HSF1). It can safely and effectively fight and treat obesity, and improve metabolic disorders such as insulin resistance and lipid deposition in the liver.
In addition, the team discovered the HSF1-A2B1 transcription axis for the first time at the genome level, further improving the HSF1 metabolic regulation network. After clinical studies of more than 10,000 people, the team clarified the association between HSF1 and metabolic traits, thus providing new targets and strategies for the intervention of obesity.
Cell working diagram (Graphic abstract)
"The work found that local hyperthermia can accurately activate the HSF1 signaling pathway in beige fat, promote thermogenesis, and do not affect the sympathetic nervous system or immune system, indicating the convenience, safety and effectiveness of the method in weight loss, which may become a new target for obesity treatment in the future, and may also develop related wearable devices to establish a new lifestyle against metabolic chronic diseases." Ning Guang, an academician of the Chinese Academy of Engineering and Ruijin Hospital, commented.
As a means of treatment, heat therapy has been around for a long time. However, systemic hyperthermia may increase the risk of neurological and cardiovascular disease, and it is unclear whether beige fat is involved in hyperthermia metabolism. The application of PET-CT technology in 2009 showed for the first time that beige fat is distributed on both sides of the neck, upper back, near the collarbone and around the spine in adults, which has the effect of sensing cold and enhancing sugar absorption and metabolism.
Cold stimulation or β adrenoceptor agonists are effective methods of activating beige fats, but these methods have a limited effect in the human body and may have potential side effects that can be harmful to health. Therefore, there is an urgent need to discover new targets and new strategies to activate beige fat in a safe and effective way to fight obesity.
The research group of Xinran Ma and Lingyan Xu has long been concerned about the close relationship between the heat shock factor HSF1 and fat metabolism. Given the nature of HSF1 being activated under thermal shock, they turned their attention to heat therapy.
Based on the previous research results, the team focused on beige fat, and jointly researcher Zhang Qiang, used beige fat injection to inject a photothermal gel based on polydopamine nanoparticles, and realized the efficient local hyperthermia of beige fat at a mild temperature (41±0.5oC) by infrared light irradiation.
Through temperature-sensitive fluorescent dyes, infrared thermography, and HSF1 fat-specific knockout mice, the researchers tested the effect of beige fat local hyperthermia on adipose tissue and overall metabolism, and found that local hyperthermia not only promoted thermogenesis of beige fat cells cultured in vitro, but also activated adipose tissue thermogenesis in mice and humans.
Moreover, the researchers confirmed that long-term local mild temperature hyperthermia can fight and treat obesity in an HSF1-dependent manner without affecting the central sympathetic nervous system and immune system, improve insulin sensitivity and liver lipid deposition, and do not produce significant side effects, indicating that local hyperthermia is a safe way to lose weight. The therapy can not only prevent and combat obesity, but also play a therapeutic role in severely obese mice.
Jia Weiping, an academician of the Chinese Academy of Engineering and the Sixth Academy of Shanghai, commented that the study innovatively found that beige fat can induce local mild thermal effects through HSF1 and activate thermogenesis, safely and effectively improve various metabolic disorders such as obesity and insulin resistance, laying an important research foundation for follow-up clinical drug research and development and precision treatment.