Plasma ceramide levels are altered in low and normal birth weight men in response to short-term high-fat overfeeding

Allan A. Vaag,Charlotte Brøns,Susanne Brix,Kristian Fog Nielsen,Amalie Ribel-Madsen,Rasmus Ribel-Madsen

doi:10.1038/s41598-018-21419-5

Abstract

Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. We hypothesised that LBW individuals exhibit an increased fatty acid flux into lipogenesis in non-adipose tissue with a resulting accumulation of lipotoxic lipids, including ceramides, in the blood. Therefore, we measured fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet by HPLC-HRMS. LBW men did not show elevated plasma ceramide levels after the control or high-fat, high-calorie diet. An increased fatty acid oxidation rate in these individuals during both diets may limit ceramide synthesis and thereby compensate for a likely increased fatty acid load to non-adipose tissue. Interestingly, LBW and NBW men decreased d18:0–18:1/d18:1–18:0 and d18:1–24:2/d18:2–24:1 levels and increased the d18:0–24:1a level in response to overfeeding. Plasma d18:0–24:1a and total ceramide levels were positively associated with the fasting blood glucose level and endogenous glucose production after the control diet, and the total ceramide level was in addition positively associated with hepatic insulin resistance. Further studies are needed to determine if lipotoxicity contributes to insulin resistance in LBW individuals.

Highlights

Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes later in life compared with normal birth weight (NBW) individuals[1,2,3,4]
Obese individuals with type 2 diabetes have a higher plasma LDL-ceramide level compared with obese, insulin-sensitive individuals[19], indicating that an increased ceramide synthesis in the liver may contribute to the development of insulin resistance[20]
LBW men did not show altered fasting plasma ceramide levels after the control or high-fat, high-calorie diet intervention compared with NBW men

Summary

Introduction

Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes later in life compared with normal birth weight (NBW) individuals[1,2,3,4]. As we have shown that NBW men of the above mentioned study population develop impaired hepatic insulin sensitivity in response to 5-day high-fat overfeeding[6], our secondary aim was to investigate if lipotoxicity could be part of the adverse events leading to this. We have previously found that young, healthy, LBW men of another study population than the present display an increased whole body and adipose tissue lipolysis[7,8] This was, not linked to elevated plasma non-esterified fatty acid (NEFA) or triacylglycerol levels, suggesting that an increased uptake of fatty acids from the blood into tissues and/or an increased clearance or metabolism of fatty acids in adipose tissue could be in play. We hypothesised that LBW men have higher fasting plasma ceramide levels, including specific ceramide species and/or total ceramide, and that such changes are associated with their impaired insulin sensitivity

Methods

Results

Conclusion