Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases

Abstract

In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS), (i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.e., palmitate and stearate), influencing cellular membrane physiology and signaling, leading to broad effects on human physiology. In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment for various diseases, such as nonalcoholic steatohepatitis, Alzheimer’s disease, cancer, and skin disorders. Sterculic acid (SA) is a cyclopropene fatty acid originally found in the seeds of the plant Sterculia foetida with numerous biological activities. On the one hand, its ability to inhibit stearoyl-CoA desaturase (SCD) allows its use as a coadjuvant of several pathologies where this enzyme has been associated. On the other hand, additional effects independently of its SCD inhibitory properties, involve anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD). This review aims to summarize the mechanisms by which SA exerts its actions and to highlight the emerging areas where this natural compound may be of help for the development of new therapies for human diseases.

Determination of Cyclopropenoid Fatty Acids in Ewe Milk Fat by GC-MS after Intravenous Administration of Sterculic Acid

“…Among naturally occurring CPEFA, sterculic and malvalic acid are suggested to have several biological properties, ranging from insecticidal, antifungal, antibiotic, antiviral, herbicidal, hormonal, neurochemical, carcinogenic or antitumoral activities to enzyme and gluconeogenesis inhibitions [ 15 , 21 ]. Studies with the 3T3L1 cell line [ 25 ] suggested that CPEFA, such as sterculic and malvalic acids, inhibit Δ9-desaturase activity due to the formation of a non-dissociating enzyme-sterculoyl-CoA complex, preventing the normal desaturation, which occurs in the absence of altered transcription or translation of the Δ9-desaturase gene.…”

“…Rumenic acid is the major conjugated linoleic acid (CLA) isomer naturally present in milk and dairy products and it is well-known for its potentially health promoting properties [ 14 ]. In addition, the ability of sterculic acid to inhibit Δ9-desaturase allows a potential use of this CPEFA as a coadjutant in the treatment of several pathologies in which Δ9-desaturase might have some role (e.g., nonalcoholic steatohepatitis, cancer, and retinal disorders) [ 15 ].…”

Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids

“…Dihydrosterculic acid and sterculic acid are available in sterculia foetida (~ 50%) and cotton-seed oil (2%). The sterculia foetida oil diet for rats showed healthy effects such as reduced reproductive function, retarted growth, and weight gain (Nixon et al 1974 ; Eisele et al 1977 ; Matlock et al 1985 ; Peláez et al 2020 ). Similar impact can be anticipated for PTA as it is chemically similar to sterculic acid and shows high binding affinity against PPARγ.…”

Fatty Acids and Membrane Lipidomics in Oncology: A Cross-Road of Nutritional, Signaling and Metabolic Pathways

“…In the context of membrane therapy, we must also mention natural fatty acids with a structure able to interfere with lipid enzymes, such as sterculic acid, a cyclopropane-containing derivative of oleic acid (9,10-methylene-9-octadecenoic acid) found in plants of the genus Sterculia . This is an inhibitor of SCD-1, and of the related cascades, as previously explained, which has attracted interest for application in various diseases, including cancer [ 174 ]. As previously described, lipid enzyme inhibitors (fatty acid synthesis and desaturation) are attracting interest for innovative cancer treatments, and readers are directed to reviews to deepen the state-of-the-art of such therapeutic strategies [ 15 , 21 , 174 ].…”