Countering impaired glucose homeostasis during catch-up growth with essential polyunsaturated fatty acids: is there a major role for improved insulin sensitivity?

Julie Calonne,Isabelle Scerri,Helena Marcelino,Abdul G Dulloo,Christelle Veyrat-Durebex

doi:10.1038/s41387-020-00143-y

Abstract

Background/ObjectivesCatch-up growth, an important risk factor for later obesity and type 2 diabetes, is often characterized by a high rate of fat deposition associated with hyperinsulinemia and glucose intolerance. We tested here the hypothesis that refeeding on a high-fat diet rich in essential polyunsaturated fatty acids (ePUFA) improves glucose homeostasis primarily by enhancing insulin sensitivity in skeletal muscles and adipose tissues.MethodsRats were caloric restricted for 2 weeks followed by 1–2 weeks of isocaloric refeeding on either a low-fat (LF) diet, a high-fat (HF) diet based on animal fat and high in saturated and monounsaturated fatty acids (HF SMFA diet), or a HF diet based on vegetable oils (1:1 mixture of safflower and linseed oils) and rich in the essential fatty acids linoleic and α-linolenic acids (HF ePUFA diet). In addition to measuring body composition and a test of glucose tolerance, insulin sensitivity was assessed during hyperinsulinemic-euglycemic clamps at the whole-body level and in individual skeletal muscles and adipose tissue depots.ResultsCompared to animals refed the LF diet, those refed the HF-SMFA diet showed a higher rate of fat deposition, higher plasma insulin and glucose responses during the test of glucose tolerance, and markedly lower insulin-stimulated glucose utilization at the whole body level (by a-third to a-half) and in adipose tissue depots (by 2–5 folds) during insulin clamps. While refeeding on the ePUFA diet prevented the increases in fat mass and in plasma insulin and glucose, the results of insulin clamps revealed that insulin-stimulated glucose utilization was not increased in skeletal muscles and only marginally higher in adipose tissues and at the whole-body level.ConclusionsThese results suggest only a minor role for enhanced insulin sensitivity in the mechanisms by which diets high in ePUFA improves glucose homeostasis during catch-up growth.

Highlights

Catch-up growth has long been considered as an essential feature of recovery from the deleterious effects of perturbed growth on development and health
Using a rat model of semistarvation-refeeding which exhibits preferential catch-up fat associated with hyperinsulinaemia even in the absence of hyperphagia, we previously showed that despite insulin resistance in skeletal muscle, the animals refed on a low-fat diet achieved blood glucose homeostasis in that they show normal plasma glucose similar to those of the controls whether in the post absorptive state or in response to a glucose load[7,8]
Of particular interest was the demonstration that refeeding with diet enriched with oils rich in essential polyunsaturated fatty acids—linoleic acid and/or α-linolenic acid—prevented the excessive fat deposition and exacerbation of hyperinsulinemia and impaired glucose homeostasis observed during catch-up fat on high-fat diets high in saturated and monounsaturated fatty acids[11,12]

Summary

Introduction

Catch-up growth has long been considered as an essential feature of recovery from the deleterious effects of perturbed growth on development and health. Using a rat model of semistarvation-refeeding which exhibits preferential catch-up fat associated with hyperinsulinaemia even in the absence of hyperphagia, we previously showed that despite insulin resistance in skeletal muscle, the animals refed on a low-fat diet achieved blood glucose homeostasis in that they show normal plasma glucose similar to those of the controls whether in the post absorptive state or in response to a glucose load[7,8] This is achieved by an increase in insulin-stimulated glucose uptake in adipose tissues which, together with an enhancement in de novo lipogenesis, provide a quantitative important glucose sink[8]. Of particular interest was the demonstration that refeeding with diet enriched with oils rich in essential polyunsaturated fatty acids (ePUFA)—linoleic acid and/or α-linolenic acid—prevented the excessive fat deposition and exacerbation of hyperinsulinemia and impaired glucose homeostasis observed during catch-up fat on high-fat diets high in saturated and monounsaturated fatty acids[11,12]

Methods

Results

Conclusion