The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor <i>in vivo</i>

Bass, Joseph J.; Kazi, Abid A.; Deane, Colleen S.; Nakhuda, Asif; Ashcroft, Stephen P.; Brook, Matthew S.; Wilkinson, Daniel J.; Phillips, Bethan E.; Philp, Andrew; Tarum, Janelle; Kadi, Fawzi; Andersen, Ditte; García, Amadeo Muñoz; Smith, Kyle; Gallagher, Iain J.; Szewczyk, Nathaniel J.; Cleasby, Mark E.; Atherton, Philip J.

doi:10.1113/jp280652

Cited by 39 publications

(34 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…First, there seems to be associations between mutations in the vitamin D receptor and muscle weakness in both humans and mice 54,55 . Second, muscle‐specific knock‐out of the vitamin D receptor in mice deteriorates muscle strength and mass in a manner that resemble sarcopenia 56,57 . The prevailing uncertainty is fuelled by a seeming lack of effects of vitamin D supplementation per se on the muscle transcriptome in vitamin D‐insufficient frail elderly, although also in that study the vitamin D dosage was relatively low (400 IU/day) 58 .…”

Section: Introductionmentioning

confidence: 82%

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults

Mølmen

Hammarström

Pedersen

et al. 2021

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Lifestyle therapy with resistance training is a potent measure to counteract age‐related loss in muscle strength and mass. Unfortunately, many individuals fail to respond in the expected manner. This phenomenon is particularly common among older adults and those with chronic diseases (e.g. chronic obstructive pulmonary disease, COPD) and may involve endocrine variables such as vitamin D. At present, the effects of vitamin D supplementation on responses to resistance training remain largely unexplored. Methods Ninety‐five male and female participants (healthy, n = 71; COPD, n = 24; age 68 ± 5 years) were randomly assigned to receive either vitamin D3 or placebo supplementation for 28 weeks in a double‐blinded manner (latitude 61°N, September–May). Seventy‐eight participants completed the RCT, which was initiated by 12 weeks of supplementation‐only (two weeks with 10 000 IU/day, followed by 2000 IU/day), followed by 13 weeks of combined supplementation (2000 IU/day) and supervised whole‐body resistance training (twice weekly), interspersed with testing and measurements. Outcome measures included multiple assessments of muscle strength (nvariables = 7), endurance performance (n = 6), and muscle mass (n = 3, legs, primary), as well as muscle quality (legs), muscle biology (m. vastus lateralis; muscle fibre characteristics, transcriptome), and health‐related variables (e.g. visceral fat mass and blood lipid profile). For main outcome domains such as muscle strength and muscle mass, weighted combined factors were calculated from the range of singular assessments. Results Overall, 13 weeks of resistance training increased muscle strength (13% ± 8%), muscle mass (9% ± 8%), and endurance performance (one‐legged, 23% ± 15%; whole‐body, 8% ± 7%), assessed as weighted combined factors, and were associated with changes in health variables (e.g. visceral fat, −6% ± 21%; [LDL]serum, −4% ± 14%) and muscle tissue characteristics such as fibre type proportions (e.g. IIX, −3% points), myonuclei per fibre (30% ± 65%), total RNA/rRNA abundances (15%/6–19%), and transcriptome profiles (e.g. 312 differentially expressed genes). Vitamin D3 supplementation did not affect training‐associated changes for any of the main outcome domains, despite robust increases in [25(OH)D]serum (∆49% vs. placebo). No conditional effects were observed for COPD vs. healthy or pre‐RCT [25(OH)D]serum. In secondary analyses, vitamin D3 affected expression of gene sets involved in vascular functions in muscle tissue and strength gains in participants with high fat mass, which advocates further study. Conclusions Vitamin D3 supplementation did not affect muscular responses to resistance training in older adults with or without COPD.

show abstract

Section: Introductionmentioning

confidence: 82%

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults

Mølmen

Hammarström

Pedersen

et al. 2021

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…Visual inspection analysis showed that the hind limb size was not clearly different among groups, although the hind limb sizes of HB200 group were bigger than those of other groups. Skeletal muscle atrophy is characterized by reduction in muscle mass and diameter of muscle fiber [26]. Histological examination results of gastrocnemius cross sections showed that the diameters of muscle fiber were greater in NC and HB groups than those of HC group.…”

Section: Effects Of Hb On Muscle Mass and Expression Levels Of Atrophy Related Genesmentioning

confidence: 99%

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice

et al. 2021

View full text Add to dashboard Cite

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic obesity have not been reported yet. Thus, the aim of this study was to investigate whether HB extract might have any beneficial effects on sarcopenic obesity in high-fat diet-induced mice. Forty-eight mice were classified into six groups and treated for eight weeks: (1) NC, normal diet control; (2) HC, high-fat diet control; (3) PC, high-fat diet with orlistat; (4) HB100, high-fat diet with HB extract at 100 mg/kg; (5) HB200, high-fat diet with HB extract at 200 mg/kg; and (6) HB400, high-fat diet with HB extract at 400 mg/kg. Body weight, fat accumulation, muscle mass, muscle strength, and mRNA expression of muscle atrophy were monitored. Compared with the HC group, HB administration showed anti-obesity properties. It reduced body weight gain and modulated serum biochemical parameters and tissue antioxidant enzymes. HB also increased muscle strength and muscle mass of hind legs. In addition, it decreased mRNA expression levels of Atrogin1 and MuRF1 as markers of muscle atrophy but increased PGC1α and SIRT1 as markers of muscle growth. These results suggest that HB might be effective in preventing sarcopenia associated with obesity.

show abstract

“…Reduced vitamin D is associated with impaired mitochondrial function in skeletal muscle [ 146 ]. Moreover, vitamin D receptor (VDR) loss-of-function C2C12 myoblasts display severely compromised mitochondrial function [ 147 ], whereas muscle-specific VDR knock down in rodents leads to decreased expression of mitochondrial genes and sarcopenia [ 148 , 149 ]. On the other hand, 25(OH)D administration improves mitochondrial OXPHOS and dynamics in C2C12 myoblasts [ 146 ] ( Figure 3 ).…”

Section: Vitamin Dmentioning

confidence: 99%

From the Bench to the Bedside: Branched Amino Acid and Micronutrient Strategies to Improve Mitochondrial Dysfunction Leading to Sarcopenia

Romani

Berger

2022

Nutrients

View full text Add to dashboard Cite

With extended life expectancy, the older population is constantly increasing, and consequently, so too is the prevalence of age-related disorders. Sarcopenia, the pathological age-related loss of muscle mass and function; and malnutrition, the imbalance in nutrient intake and resultant energy production, are both commonly occurring conditions in old adults. Altered nutrition plays a crucial role in the onset of sarcopenia, and both these disorders are associated with detrimental consequences for patients (e.g., frailty, morbidity, and mortality) and society (e.g., healthcare costs). Importantly, sarcopenia and malnutrition also share critical molecular alterations, such as mitochondrial dysfunction, increased oxidative stress, and a chronic state of low grade and sterile inflammation, defined as inflammageing. Given the connection between malnutrition and sarcopenia, nutritional interventions capable of affecting mitochondrial health and correcting inflammageing are emerging as possible strategies to target sarcopenia. Here, we discuss mitochondrial dysfunction, oxidative stress, and inflammageing as key features leading to sarcopenia. Moreover, we examine the effects of some branched amino acids, omega-3 PUFA, and selected micronutrients on these pathways, and their potential role in modulating sarcopenia, warranting further clinical investigation.

show abstract

The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor in vivo

Cited by 39 publications

References 78 publications

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice

From the Bench to the Bedside: Branched Amino Acid and Micronutrient Strategies to Improve Mitochondrial Dysfunction Leading to Sarcopenia

Contact Info

Product

Resources

About

The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor in vivo

Cited by 39 publications

References 78 publications

Vitamin D3supplementation does not enhance the effects of resistance training in older adults

Vitamin D3supplementation does not enhance the effects of resistance training in older adults

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice

From the Bench to the Bedside: Branched Amino Acid and Micronutrient Strategies to Improve Mitochondrial Dysfunction Leading to Sarcopenia

Contact Info

Product

Resources

About

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults

Vitamin D₃supplementation does not enhance the effects of resistance training in older adults