Journal Article

Maternal high-fat diet in mice alters immune regulation and lung function in the offspring

Fisk, Helena L., Mercken, Lindert P., Calder, Philip C., Holloway, John W., Losol, Purevsuren, Torrens, Christopher

2021

Overview

PUFA modulate immune function and have been associated with the risk of childhood atopy and asthma. We investigated the effect of maternal fat intake in mice on PUFA status, elongase and desaturase gene expression, inflammatory markers and lung function in the offspring. C57BL/6J mice (n 32) were fed either standard chow (C, 20·4 % energy as fat) or a high-fat diet (HFD, 39·9 % energy as fat) for 4 weeks prior to conception and during gestation and lactation. At 21 d of age, offspring were weaned onto either the HFD or C, generating four experimental groups: C/C, C/HF, HF/C and HF/HF. Plasma and liver fatty acid composition were measured by GC and gene expression by quantitative PCR. Lung resistance to methacholine was assessed. Arachidonic acid concentrations in offspring plasma and liver phospholipids were increased by HFD; this effect was greater in the post-natal HFD group. DHA concentration in offspring liver phospholipids was increased in response to HFD and was higher in the post-natal HFD group. Post-natal HFD increased hepatic fatty acid desaturase (FADS) 2 and elongation of very long-chain fatty acid 5 expression in male offspring, whereas maternal HFD elevated expression of FADS1 and FADS2 in female offspring compared with males. Post-natal HFD increased expression of IL-6 and C-C motif chemokine ligand 2 (CCL2) in perivascular adipose tissue. The HFD lowered lung resistance to methacholine. Excessive maternal fat intake during development modifies hepatic PUFA status in offspring through regulation of gene expression of enzymes that are involved in PUFA biosynthesis and modifies the development of the offspring lungs leading to respiratory dysfunction.

• Publisher: Cambridge University Press
• Subject: Adipose tissue / Age / Allergies / Animals / Arachidonic acid / Arachidonic Acid - blood / Asthma / Atopy / Biosynthesis / Chemokines / childhood / Children / conception / Cytokines / Desaturase / Diet / Diet, High-Fat - adverse effects / Elongation / Energy / Enzymes / fat intake / Fatty acid composition / fatty acid desaturase / Fatty acids / Female / females / Fish oils / Gene expression / gene expression regulation / Gestation / High fat diet / Immune response / Immunoregulation / Inflammation / Interleukin 6 / Lactation / ligands / Liver / Lung - drug effects / Lung - physiopathology / lung function / Lungs / Male / males / Maternal Nutritional Physiological Phenomena / Metabolism / Metabolites / Methacholine / Methacholine Chloride - pharmacology / Mice / Mice, Inbred C57BL / Monocyte chemoattractant protein 1 / Nutritional Immunology / Obesity / Offspring / Phospholipids / Phospholipids - analysis / Plasma / Polyunsaturated fatty acids / Pregnancy / progeny / quantitative polymerase chain reaction / Respiratory function / risk / very long chain fatty acids