Obesity Augments Glucocorticoid-Dependent Muscle Atrophy in Male C57BL/6J Mice

Gunder, Laura C.; Harvey, Innocence; Redd, JeAnna R.; Davis, Carol; AL-Tamimi, Ayat; Brooks, Susan V.; Bridges, Dave

doi:10.3390/biomedicines8100420

Cited by 10 publications

(7 citation statements)

References 48 publications

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“…Another gene significantly associated with all three weight outcomes, and always with a negative sign (higher methylation inducing lower weight outcomes), was PPP1R16B. The protein encoded by PPP1R16B is phosphatase 1 ( PP1 ) regulatory inhibitory subunit 16B, 59 which is also referred to as TIMAP or ANKRD4 . 60 PP1 is involved in many essential cellular mechanisms and is part of a large interactome with over 200 interactors identified in vertebrates.…”

Section: Discussionmentioning

confidence: 99%

Methylation profiles at birth linked to early childhood obesity

Lariviere,

Craig,

Paul

et al. 2024

J Dev Orig Health Dis

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Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many “omics” factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.

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Section: Discussionmentioning

confidence: 99%

Methylation profiles at birth linked to early childhood obesity

Lariviere,

Craig,

Paul

et al. 2024

J Dev Orig Health Dis

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“…Chronic CORT treatment by drinking water may affect both the central and peripheral circadian clocks, including oscillations of gene expression; this should be addressed in future studies. Second, the significance of muscle GR signaling and related inter-organ communication might be different among catabolic models (18,52,53), nutritional states (54,55), species (56), and sexes (57)(58)(59)(60)(61). Comprehensive analyses that include an assessment of energy balance in various models at different time points should be performed to reveal conditionally determined metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

The crucial role of muscle glucocorticoid signaling in accelerating obesity and glucose intolerance via hyperinsulinemia

Yamazaki¹,

Uehara²,

Yoshikawa³

et al. 2023

JCI Insight

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Metabolic crosstalk from skeletal muscle to multiple organs is important for maintaining homeostasis, and its dysregulation can lead to various diseases. Chronic glucocorticoid administration often induces muscle atrophy and metabolic disorders such as diabetes and central obesity; however, the detailed underlying mechanism remains unclear. We previously reported that the deletion of glucocorticoid receptor (GR) in skeletal muscle increases muscle mass and reduces fat mass through muscle-liver-fat communication under physiological conditions. In this study, we show that muscle GR signaling plays a crucial role in accelerating obesity through the induction of hyperinsulinemia. Fat accumulation in liver and adipose tissue, muscle atrophy, hyperglycemia, and hyperinsulinemia induced by chronic corticosterone (CORT) treatment improved in musclespecific GR knockout (GRmKO) mice. Such CORT-induced fat accumulation was alleviated by suppressing insulin production (streptozotocin injection), indicating that hyperinsulinemia enhanced by muscle GR signaling promotes obesity. Strikingly, glucose intolerance and obesity in ob/ob mice without CORT treatment were also improved in GRmKO mice, indicating that muscle GR signaling contributes to obesity-related metabolic changes, regardless of systemic glucocorticoid levels. Thus, this study provides new insight for the treatment of obesity and diabetes by targeting muscle GR signaling.

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“…Several reports claim that dexamethasone is known to produce skeletal muscle weakness and on prolonged use causes skeletal muscle atrophy, thereby causing functional impairment of limbs as a result of cascade of mechanisms. Dexamethasone induces muscle atrophy by mediating protein catabolism and the elevation of atrophic markers in the skeletal muscle cells, thus diminishing the muscle mass development [ 18 , 19 ]. The present study was designed to study the effect of standardized M. oleifera leaf extract against dexamethasone induced skeletal muscle impairment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Moringa oleifera leaf extract on exercise and dexamethasone-induced functional impairment in skeletal muscles

Barodia

Cheruku

Kanwal

et al. 2022

Journal of Ayurveda and Integrative Medicine

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Background Chronic administration of steroids like dexamethasone produces symptoms including weight loss and skeletal muscle dysfunction. Similar events are reported in chronic or high-intensity exercises, that can lead to fatigue and muscle damage. Objective In the present study, the effect of Moringa oleifera leaf extract was evaluated against dexamethasone (Dex) and exercise (Exe)-induced muscle changes in rats. Materials and methods Six groups each containing 6 rats, namely normal, Dex control, Exe Control, Dex + M. oleifera leaf extract (300mg/kg p.o. ), Dex + Exe, Dex + Exe + M. oleifera leaf extract were assessed in the study. Dex was administered at 0.6 mg/kg i.p. daily for 7 days. Exercise was given for a total of 10 days after 30 minutes of dosing using treadmill equipment for 900 seconds at speed 18 m/min. Animals were assessed for variation in body weight, muscular endurance using treadmill, locomotor activity using actophotometer, motor coordination using rotarod on day zero, and day seven. Hemidiaphragm of rats were isolated and used for evaluation of the glucose uptake. Gastrocnemius muscle was isolated and subjected to hematoxylin and eosin staining. Results Dex and Exe control animals showed a significant decrease in skeletal muscle activity when compared to normal control animals in the actophotometer test. Improvement in endurance were seen in Dex + M. oleifera leaf extract, and Dex + exercise + M. oleifera leaf extract groups compared to Dex control group. Improvement in locomotor activity was seen in Dex group subjected to exercise and was significant when treated with M. oleifera leaf extract. Histology reports were in accordance with the functional parameters. Conclusion M. oleifera leaf extract supplemented with exercise showed a reversal in the dexamethasone-induced functional impairment in skeletal muscles.

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Obesity Augments Glucocorticoid-Dependent Muscle Atrophy in Male C57BL/6J Mice

Cited by 10 publications

References 48 publications

Methylation profiles at birth linked to early childhood obesity

Methylation profiles at birth linked to early childhood obesity

The crucial role of muscle glucocorticoid signaling in accelerating obesity and glucose intolerance via hyperinsulinemia

Effect of Moringa oleifera leaf extract on exercise and dexamethasone-induced functional impairment in skeletal muscles

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