Lactational High-Fat Diet Exposure Programs Metabolic Inflammation and Bone Marrow Adiposity in Male Offspring.

Hannah Hafner,Brigid Gregg,Mita Varghese,Devika P Bagchi,Ormond A Macdougald,Jeremy Clemente,Eric Chang,Kanakadurga Singer,Simin Abrishami,Zach Carlson,Allen Zhu

doi:10.3390/nu11061393

Hannah Hafner, Brigid Gregg + Show 9 more

Open Access

https://doi.org/10.3390/nu11061393

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Journal: Nutrients	Publication Date: Jun 21, 2019
Citations: 21	License type: CC BY 4.0

Affiliation: Michigan Medicine, University of Michigan–Ann Arbor

Abstract

Overnutrition during critical windows of development plays a significant role in life-long metabolic disease risk. Early exposure to excessive nutrition may result in altered programming leading to increased susceptibility to obesity, inflammation, and metabolic complications. This study investigated the programming effects of high-fat diet (HFD) exposure during the lactation period on offspring adiposity and inflammation. Female C57Bl/6J dams were fed a normal diet or a 60% HFD during lactation. Offspring were weaned onto a normal diet until 12 weeks of age when half were re-challenged with HFD for 12 weeks. Metabolic testing was performed throughout adulthood. At 24 weeks, adipose depots were isolated and evaluated for macrophage profiling and inflammatory gene expression. Males exposed to HFD during lactation had insulin resistance and glucose intolerance as adults. After re-introduction to HFD, males had increased weight gain and worsened insulin resistance and hyperglycemia. There was increased infiltration of pro-inflammatory CD11c+ adipose tissue macrophages, and bone marrow was primed to produce granulocytes and macrophages. Bone density was lower due to enhanced marrow adiposity. This study demonstrates that maternal HFD exposure during the lactational window programs offspring adiposity, inflammation, and impaired glucose homeostasis.

Highlights

Stressors during critical developmental windows are important contributors to lifetime metabolic disease risk [1]
When we continued to follow the male offspring on a normal diet, we found that high-fat diet (HFD)-Lac males developed insulin resistance by Insulin glucose tolerancetolerance tests (ITT) at 20 weeks (Figure 1G) with mild glucose intolerance at 22 weeks (Figure 1H)
When the male mice were put on a high-fat diet re-challenge (+HFD) at 12 weeks of age, the metabolic phenotypes observed in males on a normal diet were exacerbated

Summary

Introduction

Stressors during critical developmental windows are important contributors to lifetime metabolic disease risk [1]. With the increased prevalence of type 2 diabetes, understanding the contribution of early life stressors to lifetime metabolic disease risk may provide avenues for primary prevention. While in utero developmental programming events have been studied in detail, the early postnatal critical window is less well studied. The lactation period is an important time of development and reorganization of metabolic tissues [2,3,4]. This period can have an independent but important impact on metabolic programming [5].

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