Novel Strategies targeting Obesity and Metabolic Diseases

The 21st century features excessive food availability and prevalent sedentary lifestyle. Unsurprisingly, obesity has become one of the most serious problems threatening public health with a staggering morbidity/mortality rate. Obesity is the leading risk factor for a series of metabolic diseases, i.e. diabetes, cardiovascular disease, hypertension, non-alcoholic hepatic steatosis, osteoporosis and certain types of cancer. Although, theoretically, body weight could be easily controlled by the balance of food intake and caloric burning, the rapid and stressful pace of modern society has made the healthy life style of eating less and exercising more hard to achieve its popularity. Pharmacotherapeutic solutions targeting appetite or energy expenditure are limited and often with undesired and sometimes dangerous side effects. The problem becomes even more complicated when genetic susceptibility for obesity is taken into account. In result, till now, the long and intense battle for obesity-intervention still wages and we are in urgent need for effective weight-losing strategies.
Fortunately, we are in the middle of technological revolution. New and ground-breaking discoveries constantly emerge nowadays, providing us novel and powerful weapons in treating obesity and metabolic disorders and thus, new hope in fighting obesity. To name a few, firstly, with the help of new development in optogenetics, chemogenetics and synthetic biology, we now have a clear view of the hunger circuits controlling eating behaviors, and appetite-manipulating is achievable in animal models. In addition, these new techniques also have valuable applications in promoting proper responses of adipocytes, hepatocytes and pancreatic β-cells to metabolic cues. Secondly, numerous researches prove that, in both rodents and human, brown fat and the newly identified beige fat play vital roles in themogenesis and energy expenditure, as well as in glucose and lipid homeostasis as metabolic sinks. Understanding the regulatory mechanism within brown and beige fat and how metabolic organs crosstalk with each other to control brown fat activation and browning of white fat hold huge potential for developing new intervention strategies in metabolic diseases. Thirdly, gut microbiota, a relatively new but critical player in the battle of obesity, has been shown to not only correlate but also contribute to the pathogenesis of obesity and various metabolic diseases, probably through a myriad of metabolites they produce, although detailed mechanisms are still under active investigation. Last but not least, innovative translational treatments for obesity and metabolic diseases nurtured by basic scientific research continue to evolve. Efforts in screening and exploring new chemical compounds and active ingredients of traditional Chinese herbs that regulate novel gene targets in central and peripheral metabolic organs never stop, while the powerful genetic manipulation tool CRISPR/Cas9 system shows its great potential in clinical application by repairing genetic mutations associated with metabolic diseases.
In this Research Topic, original articles and review papers focused on the novel development in the pathophysiology, epidemiology, mechanism, treatment and targeting strategies of obesity and metabolic comorbidities are highly welcomed. Together, we would like to provide a comprehensive summary of the latest breakthrough in the metabolic field.