Lipolysis

Lipolysis is the breaking down of fats, specifically the liberation of fatty acids from storage triglycerides into the bloodstream. 2 In Ray Peat's framework, this process is not merely a metabolic convenience but a central axis of stress and disease. Peat noted that Thyroid Stimulating Hormone (TSH) itself can produce lipolysis, raising circulating free fatty acids and potentially contributing to functional hypothyroidism due to the antimetabolic effects of unsaturated fatty acids. 2 Dinkov has extended this, arguing that the primary hormones determining the activity of lipolytic enzymes are cortisol and adrenaline, and that chronically elevated lipolysis is a hallmark of metabolic dysfunction. 6

The distinction between basal and excessive lipolysis is critical. Dinkov emphasizes that there is always basal lipolysis occurring because at rest, muscles—especially the heart—primarily burn fat. 2 Roddy has clarified that interventions like aspirin or niacinamide do not systemically block this process but inhibit it to a point where it will not overwhelm the liver or other vital organs. 7 The danger arises from excessive lipolysis, which floods the bloodstream with free fatty acids, predominantly polyunsaturated fatty acids (PUFA). This surge blocks the metabolism of sugar via the Randle cycle, directly poisoning the pancreas and preventing insulin from acting on glucose transporters, thereby locking glucose out of the cell. 2

Excessive lipolysis is a primary driver of organ damage. Dinkov has detailed how fat cells undergoing stress shed not only fatty acids but also mitochondrial fragments into the bloodstream, which the organism interprets as a danger signal, activating the stress system (HPA axis) and suppressing gonadal and thyroid function. 5 This process increases reactive oxygen species (ROS) production in organs like the heart, leading to long-term damage such as fibrosis and congestive heart failure. 5 Furthermore, the liver has a fixed capacity to process fat; when lipolysis is elevated, the liver re-esterifies the excess into triglycerides and stores them internally, directly fattening the organ and causing insulin resistance. 9 The kidneys and brain are also highly susceptible to this PUFA-driven damage. 8

The link between lipolysis and cancer is established through estrogenic signaling. Dinkov has cited evidence that elevated lipolysis and its product, free fatty acids, drive breast cancer growth by directly activating estrogen receptors and increasing inflammation, while simultaneously suppressing Krebs cycle activity. 10 Conversely, lowering lipolysis reduces estrogenic signaling and abolishes cancer growth. 10 This explains why anti-lipolytic interventions like aspirin and niacinamide, which inhibit the enzyme fatty acid synthase (FAS), demonstrate strikingly lower rates of chronic diseases. 2 Dinkov notes that the drug Acipimox, a niacinamide derivative, works primarily by lowering lipolysis, which allows insulin to function properly and decreases blood glucose, demonstrating that fat, not sugar, is the fundamental metabolic problem. 11

Maintaining a low baseline lipolysis is therefore a central therapeutic goal. Dinkov suggests that increasing lean muscle mass through concentric exercise is a key strategy, as muscle acts as a sink for fatty acids, burning them at rest and preventing them from overwhelming organs. 2 He warns that one can sense excessive lipolysis by the smell of glycerol on the breath, a byproduct of triglyceride breakdown, indicating a harmful state of overexertion. 8 Populations with remarkably low baseline lipolysis, such as certain traditional tribes eating high-starch diets, exhibit high metabolic rates and low levels of stress hormones, supporting the hypothesis that keeping lipolysis low is essential for oxidizing glucose and maintaining metabolic health. 6