Triglyceride-based lipotoxicity in the pathophysiology of chronic diseases

Since the introduction of the concept of 'lipotoxicity' 30 years ago, it has become widely accepted that ectopic triglyceride deposition is a key contributor to metabolic diseases. Subsequently, clinical observations have also revealed that triglyceride deposition can occur in a wide range of tissues and organs, including liver, pancreas, kidney, bone, thyroid and sex glands. However, these ectopic triglycerides were long regarded as inert reservoirs. Recently, progress in the field has continued to demonstrate the pathogenic potential of ectopic triglycerides within their deposition sites. Thus, lipotoxicity-related disorders have been extended to include pancreatitis, renal disease, osteoporosis, hypothyroidism, and infertility. In this review, we aim to provide an updated summary on the contribution of triglyceride-based lipotoxicity to chronic diseases.