Metabolic Advantage of 25(OH)D3 versus 1,25(OH)2D3 Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting

Ping Zhou; Wai W Cheung; Alex Gonzalez; Venya Vaddi; Eduardo A Oliveira; Robert H Mak

doi:10.3390/cells11203264

Metabolic Advantage of 25(OH)D₃ versus 1,25(OH)₂D₃ Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting

Cells. 2022 Oct 17;11(20):3264. doi: 10.3390/cells11203264.

Authors

Ping Zhou^{1

2}, Wai W Cheung¹, Alex Gonzalez¹, Venya Vaddi^{1

3}, Eduardo A Oliveira^{1

4}, Robert H Mak¹

Affiliations

¹ Division of Pediatric Nephrology, Rady Children's Hospital, University of California, San Diego, CA 92093, USA.
² Department of Pediatric Nephrology and Rheumatology, Sichuan Provincial Maternity and Child Health Care Hospital and The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610031, China.
³ Integrative Biology & Physiology, University of California, Los Angeles, CA 90095, USA.
⁴ Department of Pediatrics, Health Sciences Postgraduate Program, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte 30310-100, MG, Brazil.

Abstract

Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D₃ versus 1,25(OH)₂D₃ repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D₃ (75 μg/kg/day) or 1,25(OH)₂D₃ (60 ng/kg/day) resulted in Ctns^-/- mice corrected low circulating 25(OH)D₃ or 1,25(OH)₂D₃ concentrations. While 25(OH)D₃ administration in Ctns^-/- mice normalized several metabolic parameters characteristic of cachexia as well as muscle function in vivo, 1,25(OH)₂D₃ did not. Administration of 25(OH)D₃ in Ctns^-/- mice increased muscle fiber size and decreased fat infiltration of skeletal muscle, which was accompanied by a reduction of abnormal muscle signaling pathways. 1,25(OH)₂D₃ administration was not as effective. In conclusion, 25(OH)D₃ supplementation exerts metabolic advantages over 1,25(OH)₂D₃ supplementation by amelioration of muscle atrophy and fat browning in Ctns^-/- mice.

Keywords: 1,25(OH)2D3; 25(OH)D3; adipose tissue browning; cachexia; infantile nephropathic cystinosis; muscle wasting; vitamin D insufficiency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism
Animals
Cachexia* / metabolism
Calcitriol* / pharmacology
Calcitriol* / therapeutic use
Dietary Supplements
Mice
Mice, Knockout
Muscle, Skeletal / metabolism
Muscular Atrophy / drug therapy
Muscular Atrophy / metabolism
Vitamin D / metabolism
Vitamin D / pharmacology
Vitamin D / therapeutic use

Substances

Calcitriol
25-hydroxyvitamin D
Vitamin D

Supplementary concepts

Cystinosis, Infantile Nephropathic

Grants and funding

This investigation was supported by Cystinosis Research Foundation. P.Z. was supported by the following fundings—“Chunhui Plan” Cooperative Scientific Research Project, Ministry of Education of the People’s Republic of China (HLJ2019023), 2022 Key R&D Plan of Science and Technology Department of Sichuan Province (2022YFS0149), Science and Technology Fund of Chengdu Medical College in 2021 (CYZYB21-22), Medical Research Project of Sichuan Province in 2021, Sichuan Medical Association (S21037) and Medical Research Project of Chengdu Municipal Health Commission (2022113).