Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats

Author(s):Show less -

Reis, Natany G. ; Assis, Ana P. ; Lautherbach, Natalia ; Goncalves, Dawit A. ; Silveira, Wilian A. ; Morgan, Henrique J. N. ; Valentim, Rafael R. ; Almeida, Lucas F. ; Heck, Lilian C. ; Zanon, Neusa M. ; Koike, Tatiana E. ; Santos, Audrei R. ; Miyabara, Elen H. ; Kettelhut, Isis C. ; Navegantes, Luiz C.

• Document type: Journal article
• Source: JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE; v. N/A, p. 13-pg., 2022-05-18.

Abstract

Background Fetal stage is a critical developmental window for the skeletal muscle, but little information is available about the impact of maternal vitamin D (Vit. D) deficiency (VDD) on offspring lean mass development in the adult life of male and female animals. Methods Female rats (Wistar Hannover) were fed either a control (1000 IU Vit. D3/kg) or a VDD diet (0 IU Vit. D3/kg) for 6 weeks and during gestation and lactation. At weaning, male and female offspring were randomly separated and received a standard diet up to 180 days old. Results Vitamin D deficiency induced muscle atrophy in the male (M-VDD) offspring at the end of weaning, an effect that was reverted along the time. Following 180 days, fast-twitch skeletal muscles [extensor digitorum longus (EDL)] from the M-VDD showed a decrease (20%; P < 0.05) in the number of total fibres but an increase in the cross-sectional area of IIB (17%; P < 0.05), IIA (19%; P < 0.05) and IIAX (21%; P < 0.05) fibres. The fibre hypertrophy was associated with the higher protein levels of MyoD (73%; P < 0.05) and myogenin (55% %; P < 0.05) and in the number of satellite cells (128.8 +/- 14 vs. 91 +/- 7.6 nuclei Pax7 + in the M-CTRL; P < 0.05). M-VDD increased time to fatigue during ex vivo contractions of EDL muscles and showed an increase in the phosphorylation levels of IGF-1/insulin receptor and their downstream targets related to anabolic processes and myogenic activation, including Ser (473)Akt and Ser (21/9)GSK-3 beta. In such muscles, maternal VDD induced a compensatory increase in the content of calcitriol (two-fold; P < 0.05) and CYP27B1 (58%; P < 0.05), a metabolizing enzyme that converts calcidiol to calcitriol. Interestingly, most morphological and biochemical changes found in EDL were not observed in slow-twitch skeletal muscles (soleus) from the M-VDD group as well as in both EDL and soleus muscles from the female offspring. Conclusions These data show that maternal VDD selectively affects the development of type-II muscle fibres in male offspring rats but not in female offspring rats and suggest that the enhancement of their size and fatigue resistance in fast-twitch skeletal muscle (EDL) is probably due to a compensatory increase in the muscle content of Vit. D in the adult age. (AU)

• FAPESP's process: 19/06517-1 - The effect of maternal vitamin D deficiency on offspring development and muscle protein metabolism
• Grantee: Natany Garcia Reis
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/10089-2 - Neural, hormonal and nutritional control of autophagy
• Grantee: Isis Do Carmo Kettelhut
• Support Opportunities: Research Projects - Thematic Grants