The Intersection of Cellular and Systemic Metabolism: Metabolic Syndrome in Systemic Lupus Erythematosus

Abstract

A high prevalence of metabolic syndrome (MetS) has been reported in multiple cohorts of systemic lupus erythematosus (SLE) patients, most likely as one of the consequences of autoimmune pathogenesis. Although MetS has been associated with inflammation, its consequences on the lupus immune system and on disease manifestations are largely unknown. The metabolism of immune cells is altered and overactivated in mouse models as well as in patients with SLE, and several metabolic inhibitors have shown therapeutic benefits. Here we review recent studies reporting these findings, as well as the effect of dietary interventions in clinical and pre-clinical studies of SLE. We also explore potential causal links between systemic and immunometabolism in the context of lupus, and the knowledge gap that needs to be addressed.

The potential causal association between systemic lupus erythematosus and endocrine and metabolic disorders in the East Asian population: A bidirectional two-sample Mendelian randomization study

“…29,30 Some medications used to treat SLE or T2DM also exhibit therapeutic effects on each other. 31,32 However, our study did not demonstrate a causal link between SLE and T2DM, unlike previous observational studies. This disparity might arise from our focus on the East Asian population and the absence of investigations among other populations.…”

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression

“…This result suggested that cholesterol biosynthesis activated IL6-STAT3 signaling. Consistent with a recent report that serum starvation conditions enhanced cholesterol biosyn-thesis [41], we expounded on the function of starvation in the manipulation of IL6 signaling by ADAM9. Rapidly proliferating cancer cells require sufficient cholesterol metabolites to support and maintain growth, survival, energy consumption, and signal transduction [42].…”

Insights into future management of lupus nephritis

“…Additionally, standard immunosuppressive treatments are linked to significant toxicities, including myelosuppression and infections (44). The use of glucocorticoids has greatly improved survival in patients with LN; however, long-term use is associated with safety concerns, including infections, elevated risk of cardiovascular disease, metabolic side effects (45), and accrual of damage from SLE, which are major causes of morbidity and mortality in SLE (5,(46)(47)(48)(49). Hence, treatment strategies that aim to minimize glucocorticoid exposure while maintaining treatment efficacy have substantial clinical value (45).…”