Core Viewpoint - The article discusses the biological mechanisms behind weight gain in middle age, particularly focusing on the role of a specific type of fat precursor cell (CP-A) that becomes more active with aging, leading to increased visceral fat accumulation [7][12][24]. Summary by Sections Mechanisms of Weight Gain - Traditional views suggest that fat cell numbers remain constant after adulthood, with weight gain primarily due to the enlargement of existing fat cells. However, recent studies indicate that new fat cells are generated in significant numbers, especially in middle-aged individuals [9][10]. Discovery of CP-A Cells - Researchers identified a specific type of fat precursor cell, CP-A, which becomes predominant in visceral fat as individuals age. In middle-aged mice, CP-A cells constituted 34.23% of the visceral white fat tissue, indicating a shift in the cellular composition of fat tissue [12][15]. Implications of Increased Visceral Fat - The accumulation of visceral fat, coupled with a decrease in muscle mass, can lead to sarcopenic obesity, where individuals may appear to have a normal BMI but suffer from metabolic disorders due to fat distribution [13][24]. CP-A Cell Characteristics - CP-A cells exhibit enhanced proliferation and differentiation capabilities compared to younger fat precursor cells. They are 2.5 times more proliferative and produce significantly more mature fat cells [17][19]. Targeting LIFR for Intervention - The LIFR (leukemia inhibitory factor receptor) pathway was identified as a potential target for controlling the proliferation of CP-A cells. Inhibition of LIFR significantly reduced fat generation in CP-A cells while having minimal effect on younger cells [20][22][23]. Conclusion on Middle-Aged Fat Gain - The increase in visceral fat in middle age is attributed to the emergence of new fat cells, particularly CP-A cells, which are regulated by the LIFR-JAK-STAT3 signaling pathway. Targeting this pathway may offer new strategies for managing stubborn fat in middle-aged individuals [24][25].