Obesity from the perspective of the liver.

Glucose is at the center of liver metabolism, and together with NADPH, it is an essential factor in hepatic regulation and adaptation to different metabolic states. The liver plays a fundamental role in the development of obesity. Excess food intake, particularly excess glucose, primarily burdens liver metabolism. The hepatocyte-specific glycogenoreticular system, a functional unit based on the tight interaction between glycogen particles and the ER, is central to the storage and distribution of glucose throughout the body. Additionally, the liver converts excess glucose into ketogenic molecules. The liver is the most important site for glucogenic to ketogenic conversion in the body. However, the escape route offered by unrestricted fatty acid synthesis and deposition takes its toll in the long run. An NADPH pool is also a pivotal connection among intermediary metabolism, redox homeostasis, and drug metabolism in hepatocytes. Preservation and recovery of excess glucose is a commitment, which presents a potential pitfall. Overfeeding can lead to pathological consequences by disrupting regulatory mechanisms. The fulfillment of metabolic goals by the liver plays a significant role in the development of various pathological conditions, such as fatty liver, obesity, insulin resistance, and metabolic syndrome.