Vitamin D deficiency serves as a precursor to stunted growth and central adiposity in zebrafish

Megan M Knuth,Debin Wan,Debabrata Mahapatra,Bruce D Hammock,Mac Law,Seth W Kullman,Dereje Jima

doi:10.1038/s41598-020-72622-2

Megan M Knuth, Debin Wan + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-72622-2

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Abstract

Emerging evidence demonstrates the importance of sufficient vitamin D (1α, 25-dihydroxyvitamin D3) levels during early life stage development with deficiencies associated with long-term effects into adulthood. While vitamin D has traditionally been associated with mineral ion homeostasis, accumulating evidence suggests non-calcemic roles for vitamin D including metabolic homeostasis. In this study, we examined the hypothesis that vitamin D deficiency (VDD) during early life stage development precedes metabolic disruption. Three dietary cohorts of zebrafish were placed on engineered diets including a standard laboratory control diet, a vitamin D null diet, and a vitamin D enriched diet. Zebrafish grown on a vitamin D null diet between 2–12 months post fertilization (mpf) exhibited diminished somatic growth and enhanced central adiposity associated with accumulation and enlargement of visceral and subcutaneous adipose depots indicative of both adipocyte hypertrophy and hyperplasia. VDD zebrafish exhibited elevated hepatic triglycerides, attenuated plasma free fatty acids and attenuated lipoprotein lipase activity consistent with hallmarks of dyslipidemia. VDD induced dysregulation of gene networks associated with growth hormone and insulin signaling, including induction of suppressor of cytokine signaling. These findings indicate that early developmental VDD impacts metabolic health by disrupting the balance between somatic growth and adipose accumulation.

Highlights

Emerging evidence demonstrates the importance of sufficient vitamin D (1α, 25-dihydroxyvitamin D3) levels during early life stage development with deficiencies associated with long-term effects into adulthood
Zebrafish grown on a vitamin D null diet between 2–12 mpf exhibited significantly stunted somatic growth and central adiposity. These findings indicate that early developmental vitamin D deficiency (VDD) impacts metabolic health by disrupting the balance between somatic growth and adipose accumulation and suggests a unique linkage between vitamin D, VDD, and metabolic homeostasis
We found that compared to the vitamin D sufficient cohort, VDD zebrafish had significantly attenuated total volume (78.33 ± 5.50 mm[3] VDD versus 209.0 ± 50.17 mm[3] VD3 Sufficient), bone volume (2.01 ± 0.43 mm[3] VDD versus 7.12 ± 2.70 mm[3] VD3 Sufficient), whole fish density (− 41.39 ± 3.04HU VDD versus − 30.15 ± 2.55HU VD3 Sufficient), bone density

Summary

Introduction

Emerging evidence demonstrates the importance of sufficient vitamin D (1α, 25-dihydroxyvitamin D3) levels during early life stage development with deficiencies associated with long-term effects into adulthood. VDD induced dysregulation of gene networks associated with growth hormone and insulin signaling, including induction of suppressor of cytokine signaling These findings indicate that early developmental VDD impacts metabolic health by disrupting the balance between somatic growth and adipose accumulation. Several recent studies demonstrate a correlation between low maternal vitamin D levels during pregnancy and small gestational size followed by high BMI’s at one and three years of age[25] These studies provide initial evidence for an inverse relationship between maternal vitamin D levels and adverse metabolic health outcomes in offspring including excess adiposity and insulin resistance; not all studies have demonstrated a definite relationship between VDD and cardiometabolic risk factors in o ffspring[6]

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