Lipid Metabolism: Immune Regulation and Therapeutic Prospectives in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by the production of abnormal autoantibodies and immune complexes that can affect the organ and organ systems, particularly the kidneys and the cardiovascular system. Emerging evidence suggests that dysregulated lipid metabolism, especially in key effector cells, such as T cells, B cells, and innate immune cells, exerts complex effects on the pathogenesis and progression of SLE. Beyond their important roles as membrane components and energy storage, different lipids can also modulate different cellular processes, such as proliferation, differentiation, and survival. In this review, we summarize altered lipid metabolism and the associated mechanisms involved in the pathogenesis and progression of SLE. Furthermore, we discuss the recent progress in the role of lipid metabolism as a potential therapeutic target in SLE.

Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

“…From FinnGen, all 953 endpoints of the following categories (ICD-10 Chapter listed in parentheses if available) were included: ‘cardiometabolic endpoints’, ‘diabetes endpoints’, ‘diseases marked as autoimmune origin’, ‘drug purchase endpoints’, ‘gastrointestinal endpoints’, ‘neoplasms from hospital discharge’ (II), ‘neoplasms from cancer register’ (II), ‘diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism’ (III), ‘endocrine nutritional and metabolic diseases’ (IV), ‘diseases of the nervous system’ (VI), ‘diseases of the circulatory system’ (IX), ‘neurological endpoints’, ‘diseases of the digestive system’ (XI). These ICD-10 chapters were chosen because diseases within these chapters have been previously reported to be associated with changes in lipid metabolism, such as II: breast cancer [75], III: Systemic Lupus Erythematosus [76], IV: lipid metabolism disorders and diabetes mellitus [77], VI: Alzheimer’s disease [78], IX: Coronary artery disease [35], XI: Nonalcoholic Fatty Liver Disease [79]. For all endpoints at least 50 cases exist.…”

Orchestrated Action of AMPK Activation and Combined VEGF/PD-1 Blockade with Lipid Metabolic Tunning as Multi-Target Therapeutics against Ovarian Cancers

“…Recently, it has been disclosed that various sub-clones of metastatic ovarian cancer cells exhibited increased aggressiveness in the ascites microenvironment via reprogramming fatty acid metabolism [ 23 ]. Since lipid metabolism can remodel the immune function and sensitivity to ferroptosis [ 97 , 98 ], additional strategies are required to determine whether combined AMPK activation with targeting lipid metabolism signalings and ferroptosis is an effective anti-cancer therapy.…”

Lipidomics Changes in a Murine Model of Neuropsychiatric Lupus

“…number of studies are finding changes in lipid metabolism in SLE. [19][20][21][22] However, unlike other affected organs, the main understanding of the mechanisms of NPSLE development is currently focused on the disruption of the blood-brain barrier and the production of brain-reactive autoantibodies. 13,23,24 Alterations in metabolism and NPSLE manifestations are currently less studied but are known to be significantly correlated.…”