Obesity is an important aspect of the metabolic syndrome and is often associated with chronic inflammation. In this context, inflammation of organs participating in energy homeostasis (such as liver, adipose tissue, muscle and pancreas) leads to the recruitment and activation of macrophages, which secrete pro-inflammatory cytokines. Interleukin-1β secretion, sustained C-reactive protein plasma levels and activation of the NLRP3 inflammasome characterize this inflammation. The Stearoyl-CoA desaturase-1 (SCD1) enzyme is a central regulator of lipid metabolism and fat storage. This enzyme catalyzes the generation of monounsaturated fatty acids (MUFAs)—major components of triglycerides stored in lipid droplets—from saturated fatty acid (SFA) substrates. In this review, we describe the molecular effects of specific classes of fatty acids (saturated and unsaturated) to better understand the impact of different diets (Western versus Mediterranean) on inflammation in a metabolic context. Given the beneficial effects of a MUFA-rich Mediterranean diet, we also present the most recent data on the role of SCD1 activity in the modulation of SFA-induced chronic inflammation.
The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment.
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