EPA and DHA inhibit LDL-induced upregulation of human adipose tissue NLRP3 inflammasome/IL-1β pathway and its association with diabetes risk factors

• Published in: Scientific reports Vol. 14; no. 1; pp. 27146 - 16
• Main Authors: Lamantia, Valérie, Bissonnette, Simon, Beaudry, Myriam, Cyr, Yannick, Rosiers, Christine Des, Baass, Alexis, Faraj, May
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/256/2515; 692/163/2743/137/773; 692/308/575; 692/700/459/1994; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adult; Beta cells; Blood; Body fat; Cholesterol; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic Acid - pharmacology; Fat metabolism; Female; Health risks; Human adipose tissue; Humanities and Social Sciences; Humans; IL-1β; Inflammasomes; Inflammasomes - metabolism; Interleukin 1; Interleukin-1beta - metabolism; Lipopolysaccharides; Lipoproteins; Lipoproteins, LDL - blood; Lipoproteins, LDL - metabolism; Low density lipoprotein; Macrophages; Male; Marine-source omega-3 fatty acids; Middle Aged; multidisciplinary; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome and interleukin-1 beta; Plasma apoB; Risk Factors; Science; Science (multidisciplinary); Signal Transduction - drug effects; Type 2 diabetes; Up-regulation; Up-Regulation - drug effects; Type 2 diabetes; Marine-source omega-3 fatty acids; Plasma apoB; NLRP3 inflammasome and interleukin-1 beta; Human adipose tissue
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-73672-6

Elevated numbers of atherogenic lipoproteins (apoB) predict the incidence of type 2 diabetes (T2D). We reported that this may be mediated via the activation of the NLRP3 inflammasome, as low-density lipoproteins (LDL) induce interleukin-1 beta (IL-1β) secretion from human white adipose tissue (WAT) and macrophages. However, mitigating nutritional approaches remained unknown. We tested whether omega-3 eicosapentaenoic and docosahexaenoic acids (EPA and DHA) treat LDL-induced upregulation of WAT IL-1β-secretion and its relation to T2D risk factors . Twelve-week intervention with EPA and DHA (2.7 g/day, Webber Naturals) abolished baseline group-differences in WAT IL-1β-secretion between subjects with high-apoB (N = 17) and low-apoB (N = 16) separated around median plasma apoB. Post-intervention LDL failed to trigger IL-1β-secretion and inhibited it in lipopolysaccharide-stimulated WAT. Omega-3 supplementation also improved β-cell function and postprandial fat metabolism in association with higher blood EPA and mostly DHA. It also blunted the association of WAT NLRP3 and IL1B expression and IL-1β-secretion with multiple cardiometabolic risk factors including adiposity. Ex vivo , EPA and DHA inhibited WAT IL-1β-secretion in a dose-dependent manner. In conclusion, EPA and DHA treat LDL-induced upregulation of WAT NLRP3 inflammasome/IL-1β pathway and related T2D risk factors. This may aid in the prevention of T2D and related morbidities in subjects with high-apoB. Clinical Trail Registration ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects with High Number of Particles That Carry “Bad Cholesterol” in the Blood – Full Text View - ClinicalTrials.gov.