Figure 1.

Vicious circles of white adipose tissue (WAT) abnormal cell growth and proliferation, and fat mass metastases. In obesity, the brain becomes less sensitive to the satiety hormone leptin, and this favors feelings of hunger and increases food intake. This further boosts the positive energy balance, induces intestinal flora dysbiosis and augments gut permeability to the bacterial endotoxin lipopolysaccharide (LPS), which is highly inflammatory. LPS inhibits the differentiation of preadipocytes to mature fat cells. Thus, more preadipocytes are formed to generate new adipocytes to store the body’s excess of energy, which enhances obesity by hyperplasia. The inhibition of adipogenesis induces mature adipocytes to undergo extreme abnormal cell growth to pack lipids that surpass their maximum storage capacity through excessive hypertrophy. This further causes hypoxia, fibrosis, and eventually cell necrosis. Massive WAT hypertrophy might induce severe hypoxia that can trigger angiogenesis, which, however, generates fragile and dysfunctional capillaries that further boost tissue inflammation. The dead adipocytes attract immune cells—macrophages—to form inflammatory crown-like structures. The affected WAT secretes high leptin levels to the brain to reduce food intake; however, the brain becomes insensitive to leptin due to the ongoing processes of obesity. WAT in the obese organism further secrets inflammatory cytokines to promote the inflammatory reaction in a chain of vicious circles that devastates WAT structure and function. This leads to lipid storage in other organs, like skeletal muscles and vital organs such as the heart, the liver, the kidneys, and the pancreas. Such expansion of WAT localization through ectopic fat depositions that embody “metastases” alters these organs functionality and therefore whole-body homeostasis. In addition, accumulated free fatty acids in blood circulation may injure endothelial cells through provoking oxidative and inflammatory reactions, which might hasten atherosclerotic plaque rupture. This can cause venous or arterial thromboembolism, which can present fatal consequences when affecting vital organs, such as in pulmonary embolism, heart attack, and stroke. These biological alterations are accompanied by those starting from a mechanical origin, such as body weight pressure on the bones and joints or airway blockage, to induce osteoarthritis or obstructive sleep apnea, respectively. These crab (cancer)-leg-like projections of cell growth, cell proliferation, and fat ectopic depositions, and their impact on the whole body in obesity, justly present high similarity with cancer disease metastases. Created with BioRender.com and with MindtheGraph.com. Accessed on 24 March 2022.