What is the clinical evidence from this study?

Study design: Other. Population: Type 2 diabetes risk factors (n=40). Intervention: EPA and DHA vs. Baseline (pre-intervention). Primary outcome: Difference in WAT IL-1β-secretion between high-apoB and low-apoB subjects.

November 7, 2024Open Access

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

VLValérie LamantiaDiabetes Canada SBSimon BissonnetteAgriculture and Agri-Food Canada MBMyriam BeaudryMontreal Clinical Research Institute

Key Result

A 12-week supplementation with 2.7 g/day of EPA and DHA abolished baseline group-differences in WAT IL-1β-secretion between subjects with high and low apoB and inhibited LDL-induced WAT IL-1β-secretion.

Structured PICO

Does EPA and DHA supplementation reduce LDL-induced upregulation of white adipose tissue IL-1β-secretion in subjects with high apoB?

Population

40 sedentary adults aged 45-74 years with a BMI > 20 kg/m2, stratified by baseline plasma apoB levels, who completed a 12-week supplementation with EPA and DHA.

Intervention

Omega-3 eicosapentaenoic and docosahexaenoic acids (EPA and DHA) 2.7 g/day for 12 weeks

Outcome

White adipose tissue (WAT) IL-1β-secretionsurrogate

EPA and DHA supplementation inhibits LDL-induced WAT IL-1β secretion and improves metabolic parameters, suggesting a potential mechanism to reduce type 2 diabetes risk in individuals with high apoB.

Limitations

Assessed risk factors for, and not the incidence of, T2D
Site of WAT used (hip) may have specific effects

Abstract

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.

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