Systemic lupus erythematosus (SLE) has been recognized as a major threat to human health, and its disease burden has attracted global attention, with an estimated global incidence of SLE being 5.14 (1.4–15.3) per 100,000 person-years[1]. SLE is a chronic autoimmune disease characterized by a dysregulated innate and adaptive immune response to autoantigens, resulting in the production of pathogenic autoantibodies and the formation of immune complexes (ICs) that cause damage to multiple tissues and organs, including the kidneys, skin, joints, blood and nervous system. The etiology of SLE is multifactorial and arising from a sophisticated interplay among genetic predispositions, epigenetic modifications, socio-economic determinants, and environmental factors[2]. Despite ongoing research efforts, the exact pathogenesis and progression of SLE have not been fully clarified.

Over the past decades, immunometabolism research has provided crucial insights into the metabolic process that immunocytes undergo after activation[3]. Immunocytes respond to stimulation by rapidly activation and differentiating into highly specialized effector cells. These activities are highly energy-intensive, necessitating not only the increased uptake of nutrients such as glucose, fatty acids, and glutamine, but also a shift in metabolic pathways to synthesize essential biological molecules like nucleic acids, lipids, proteins. These components are crucial for various cellular functions including proliferation, differentiation, secretion of pro-inflammatory cytokines, phagocytosis and tissue migration. More importantly, impaired metabolic reprogramming can directly contribute to the worsening of abnormal immune responses. Previous studies have shown that immune cells from SLE patients are deficient in several key metabolic pathways, and metabolic disorders in SLE patients may result from abnormal immune regulation and could be involved in the pathological process of the disease[4]. Therefore, studying immune cell metabolism in SLE patients has become a topic of interest. A better understanding of the abnormal metabolism of immunocytes in the disease would help improve the treatment of SLE. Moreover, the overall nutrient availability and utilization by the organism also affect the metabolic processes of immunocytes, indirectly impacting their function. From a clinical point of view, SLE patients have a generalized disturbance of energy metabolism with hypoproteinemia, hyperlipidemia, and an increased risk of atherosclerotic cardiovascular disease and diabetes. Metabolic syndrome (MetS) has been found to be more common in SLE patients than in healthy individuals, with a prevalence of up to 26 % in SLE, further exacerbating symptoms and creating a vicious cycle[5], [6].

In this review, we overview the characteristics of metabolic disorders in SLE and discuss the impact of several energy metabolism pathways on the development and progression of SLE. Furthermore, we summarize the current therapeutic strategies targeting energy metabolism pathways for SLE, offering insights for future directions in the field.