High‐fat diet‐dependent increase in plasma immunoglobulin levels are repressed by aldehyde dehydrogenase1 a1

Abstract

Abnormal immunoglobulin (Ig) production underlines hematological cancers. Studies show association of these cancers with obesity. However, it is unclear how high‐fat (HF) diets influence Ig levels in the circulation. We used six 59 weeks‐old C57BL/6 mice (wild type WT), fed a diet of 5.67% by calorie of saturated fat, compared to six age and sex‐matched WT mice fed a HF diet of 45% by calorie saturated fat for 42 weeks. Using ELISA we quantified Ig classes (IgG1, IgG2a, IgG2b, IgG3, IgA, IgM, Igκ and Igλ) in the plasma of both groups. The intra and inter‐assay variations of the ELISA assay were 2–12% and 5–30% respectively. Mice fed regular and HF diets have similar proportions of Ig's with exception of a 9% increase in IgLκ in HF diets. There was a quantitative increase of 200% to over 500% in Ig's of every class present in plasma from mice on HF diets. However, the increase in Ig production on a HF diet was suppressed by retinoic acid‐generating enzyme aldehyde dehydrogenase 1a1 (Aldh1a1). We studied this relationship in Aldh1a1−/− mice (n=6) vs. WT (n=6) mice on HF diets. Aldh1a1 −/− mice exhibited an increase in plasma Ig's: IgG1 224%, IgG2a 978%, IgG2b 106%, IgG3 217%, IgA 156%, IgLλ 105%. We confirmed polyclonal gammopathy in Aldh1a1−/− compared to WT mice on HF diet using serum protein electrophoresis. We conclude that dietary fat content increases Ig concentration in plasma dependent on the expression of Aldh1a1 enzyme.