Scientists have long believed that effector cells in the immune system are defense cells against tumors and infectious diseases, while regulatory cells act primarily in sensitization and autoimmune responses. In recent years, many studies have shown that immune cells also have a number of non-traditional immune roles, including involvement in the development of neurodegenerative pathologies, cardiovascular diseases and metabolic diseases. A new frontier of research, immunometabolism, focuses on the interplay between immunity and metabolism in physiology and disease. The discipline is currently making remarkable progress on two fronts: on the one hand, it is newly believed that the natural or acquired immune system is involved in what were previously thought to be non-immune diseases, such as obesity, producing metabolic and immune abnormalities that can lead to susceptibility to type 2 diabetes, cardiovascular disease, cancer or neurodegenerative pathologies. On the other hand, immune cells, such as lymphocytes, are influenced by internal metabolic regulation at multiple levels. In-depth elucidation of the cellular-molecular mechanisms of immune and metabolic interactions is a pressing scientific question. I. Obesity drives non-metabolic diseases through inflammation Obesity is becoming a global epidemic. The increase of obesity and the economic level and the medical condition improve the metabolic disease accompanying, such as type 2 diabetes, fatty liver, cardiovascular disease increase proportionally. It is also associated with a number of non-metabolic diseases such as asthma, Alzheimer’s disease, and certain cancers. Inflammation connects these diseases etiologically. Obesity is considered to be a systemic state of subacute inflammation. Local inflammation of adipose tissue, as well as obesity-induced systemic inflammation may be common factors driving the disease. Some adipocytokines, such as adiponectin and leptin, are produced specifically by adipose tissue, while others may be more pro-inflammatory or anti-inflammatory factors acting in natural and acquired immune responses. Various types of inflammatory factors produced by adipocytes include tumor necrosis factor (TNF), interleukin (IL)?6, resistin, retinol-binding protein 4 (RBP?4) and related human lipocalin 2, chemokine ligand 2 (CCL2), IL?18, visfatin, and CXC chemokine 5 (CXCL5), these inflammatory factors increase with the expansion of adipose tissue, suggesting that this pro-inflammatory state is associated with obesity and is likely to produce diseases caused by chronic inflammation. Conversely, anti-inflammatory adipokines such as lipocalin, IL?10 and secretory frizzled-related protein 5 (SFRP5) decreased with the expansion of adipose tissue. Although these adipokines are produced by adipose tissue, whether they are produced by adipocytes or by invading macrophages, epithelial cells, or T lymphocytes, and the amount of adipokine production needs to be studied in depth. Similarly, it is not clear which adipokines play a major role in insulin resistance or insulin sensitivity. The role of infiltrating lymphocytes also needs to be studied in depth. Second, natural immunity and obesity and type 2 diabetes natural immunity has been proved to play an important role in systemic inflammation-related obesity and other diseases. toll-like receptor (TLR) from the cellular molecular mechanism to link obesity and inflammation. tlr is the main receptor of the body to identify foreign or intrinsic pathogens. tlr4 is the first to be found to identify saturated fatty acids and to link insulin resistance with natural immunity. Currently, TLR2, TLR5 and TLR9 have been shown to play important roles in diseases such as obesity and type 2 diabetes. The specific expression of myeloid differentiation protein 88 (MyD88), a key downstream molecule of the TLR4 and TLR9 signaling pathways, in the central nervous system has also been shown to be essential for fatty acid-induced leptin resistance and obesity due to high-fat diets. Third, acquired immunity and obesity and type 2 diabetes Is acquired immunity in obesity and type 2 diabetes play a key role? Obesity, type 2 diabetes is autoimmune disease? These issues are still controversial. Autoimmune diseases must have at least the following characteristics: (1) loss of immune tolerance to specific antigens; (2) importation of pathogenic immune cells or antibodies into healthy individuals can replicate the disease process; (3) immunosuppression or immunomodulation can regulate the natural course of the disease; (4) an autoimmune etiology has been demonstrated in animal models (e.g., importation of immune cells can be used to induce disease); (5) the disease has been been shown to be associated with autoimmune genes, such as human leukocyte antigens (HLA). The presence of T lymphocytes in adipose tissue has been demonstrated in studies in obese mice, and obesity and insulin resistance can be alleviated by blocking T lymphocytes with CD3 monoclonal antibodies; T lymphocytes, B lymphocytes, monocytes, and macrophages have been shown to play an important immunological role in animal models and human adipose tissue. In addition, immune cells also play an important role in the formation and differentiation of brown adipose tissue. Although T lymphocytes have been reported to be activated in the peripheral blood of type 2 diabetic patients, some experts question that they are not using specific antigens and therefore a non-specific immune response occurs. Although it is not clear whether type 2 diabetes is an autoimmune disease, it is clear that it is different from the autoimmune response in classical type 1 diabetes. IV. Theory and practice of immunometabolism The emerging field of immunometabolism research is increasingly showing its important influence. In terms of theoretical exploration, questions that should be further investigated in depth are: Are obesity and inflammation concomitant or causal? What are their common signaling pathways? Which signaling pathways contribute to inflammation and its downstream development of type 2 diabetes, cardiovascular disease and other diseases? What are the effects of genetic and environmental factors on immunometabolic abnormalities? In terms of practical applications, relevant drugs are being developed and clinical trials are being conducted. For example, the findings that metformin, a type 2 diabetes treatment, may have antitumor effects, and that one aspirin daily has the potential effect of reducing cancer mortality, support the immunometabolic theory. In addition, several clinical studies have successively identified inflammation as a target for type 2 diabetes treatment, e.g., clinical studies of IL?1 receptor blockers have shown positive results, and salicylates have been applied to hypoglycemic treatment of obesity, both of which are currently undergoing large clinical trials. An initial clinical trial of TNF blockers in patients with type 2 diabetes did not show glucose-lowering effects, but they showed promising immunomodulatory effects in non-diabetic patients. Further, attempts to apply cellular immunomodulation in the treatment of obesity and type 2 diabetes present potential value. Thus, it is clear that immunometabolism is a new direction worthy of attention in obesity and type 2 diabetes research.