Vitamin D Deficiency Leads to Obesity, Stunted Growth in Zebrafish

Using a zebrafish model, researchers from North Carolina State University have found that vitamin D deficiency during early development can disrupt the metabolic balance between growth and fat accumulation. The results suggest a linkage between vitamin D and metabolic homeostasis, or equilibrium.

The research team, led by Seth Kullman, professor of biological sciences at NC State, looked at groups of post-juvenile zebrafish on one of three diets: no vitamin D (or vitamin D null), vitamin D enriched and control. The zebrafish spent four months on their particular diet, then the researchers looked at their growth, bone density, triglyceride, lipid, cholesterol and vitamin D levels. They also examined key metabolic pathways associated with fat production, storage and mobilization and growth promotion.

The zebrafish in the vitamin D deficient group were, on average, 50% smaller than those in the other two groups, and they had significantly more fat reserves.

“The vitamin D deficient zebrafish exhibited both hypertrophy and hyperplasia – an increase in both the size and number of fat cells,” Kullman says. “They also had higher triglycerides and cholesterol, which are hallmarks of metabolic imbalance that can lead to cardio-metabolic disease. This, combined with the stunted growth, indicates that vitamin D plays an important role in the ability to channel energy into growth versus into fat storage.”

After the initial testing, the vitamin D deficient zebrafish were given a vitamin D enriched diet for an additional six months, to see if the results could be reversed. While the fish did continue to grow and begin to utilize fat reserves, they never caught up in size with the other cohorts and they retained residual fat deposits.

“This work shows that vitamin D deficiency can influence metabolic health by disrupting the normal balance between growth and fat accumulation,” Kullman says. “Somehow the energy that should be going toward growth is getting shunted into creating fat and lipids, and this occurrence cannot be easily reversed. While we don’t yet understand the mechanism, we are beginning to tease that out.”

Future work will involve looking at the offspring of vitamin D deficient mothers, to determine whether this vitamin deficiency has epigenetic effects that can be passed down.

The research appears in Scientific Reports and is supported by the Environmental Protection Agency (STAR RD-83342002) and the National Institute of Environmental Health Sciences (grants T32 ES07046, P30ES025128, R35ES030443 and P42ES004699). Kullman is corresponding author. Megan Knuth, former NC State Ph.D. student currently at the University of North Carolina Chapel Hill, is first author. Debin Wan and Bruce Hammock, both from the University of California Davis, also contributed to the work.

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Note to editors: An abstract follows.

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

DOI: 10.1038/s41598-020-72622-2

Authors: Megan M. Knuth, Debabrata Mahapatra, Dereje Jima, Mac Law, Seth W. Kullman, North Carolina State University; Debin Wan, Bruce Hammock, University of California Davis
Published: Online Sept. 29, 2020 in Scientific Reports

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.

This post was originally published in NC State News.