Sphingolipid metabolism in brain insulin resistance and neurological diseases

Abstract

Sphingolipids, as members of the large lipid family, are important components of plasma membrane. Sphingolipids participate in biological signal transduction to regulate various important physiological processes such as cell growth, apoptosis, senescence, and differentiation. Numerous studies have demonstrated that sphingolipids are strongly associated with glucose metabolism and insulin resistance. Insulin resistance, including peripheral insulin resistance and brain insulin resistance, is closely related to the occurrence and development of many metabolic diseases. In addition to metabolic diseases, like type 2 diabetes, brain insulin resistance is also involved in the progression of neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. However, the specific mechanism of sphingolipids in brain insulin resistance has not been systematically summarized. This article reviews the involvement of sphingolipids in brain insulin resistance, highlighting the role and molecular biological mechanism of sphingolipid metabolism in cognitive dysfunctions and neuropathological abnormalities of the brain.

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

“…Altered Cer levels are detected in several pathophysiological conditions including cancer ( Brachtendorf et al, 2019 ), diabetes ( Hammad et al, 2022 ; Hammad and Lopes-Virella, 2023 ), obesity ( Raichur et al, 2019 ), Parkinson’s disease ( Abbott et al, 2014 ), and other neurological disorders ( Tomasello et al, 2022 ). Sphingolipids are also implicated in insulin resistance in the brain which is linked to metabolic and neurodegenerative diseases ( Mei et al, 2023 ). Postmortem brain tissues of the anterior cingulate cortex in patients with Parkinson’s disease showed elevated levels of shorter chain-length sphingolipid species and corresponding elevation of CerS1 transcript ( Abbott et al, 2014 ).…”

A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer’s disease, and their co-morbidities

“…An imbalance in ceramide metabolism can lead to various chronic diseases, including metabolic, cardiovascular, autoimmune and neurodegenerative diseases ( Pilátová et al, 2023 ). Recent studies have shown that ceramides and their metabolites play key roles in metabolic diseases such as AD, T2DM and neurodegenerative diseases, such as insulin and IGF-1 ( Mei et al, 2023 ). With the aging population, the global prevalence of T2DM and AD is markedly increasing.…”