scholarly journals Vitamin D repletion ameliorates adipose tissue browning and muscle wasting in infantile nephropathic cystinosis‐associated cachexia

2019 ◽  
Vol 11 (1) ◽  
pp. 120-134 ◽  
Author(s):  
Wai W. Cheung ◽  
Sheng Hao ◽  
Zhen Wang ◽  
Wei Ding ◽  
Ronghao Zheng ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Muscle Wasting ◽  
Nephropathic Cystinosis ◽  
Tissue Browning

scholarly journals A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1954
Author(s):  
Alex Gonzalez ◽  
Wai W. Cheung ◽  
Elliot A. Perens ◽  
Eduardo A. Oliveira ◽  
Arieh Gertler ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Energy Homeostasis ◽  
Muscle Wasting ◽  
Leptin Receptor ◽  
Nephropathic Cystinosis ◽  
Muscle Genes ◽  
Muscle Fat Infiltration ◽  
And Control ◽  
Tissue Browning

Mice lacking the functional cystinosin gene (Ctns−/−), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns−/− mice. We treated 12-month-old Ctns−/− mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns−/− mice. PLA attenuated adipose tissue browning in Ctns−/− mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns−/− mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns−/− mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns−/− mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.

scholarly journals Muscle wasting and adipose tissue browning in infantile nephropathic cystinosis

2015 ◽  
Vol 7 (2) ◽  
pp. 152-164 ◽  
Author(s):  
Wai W. Cheung ◽  
Stephanie Cherqui ◽  
Wei Ding ◽  
Mary Esparza ◽  
Ping Zhou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Muscle Wasting ◽  
Nephropathic Cystinosis ◽  
Tissue Browning

scholarly journals Targeting interleukin-1 for reversing fat browning and muscle wasting in infantile nephropathic cystinosis

2021 ◽  
Author(s):  
Wai W Cheung ◽  
Sheng Hao ◽  
Ronghao Zheng ◽  
Zhen Wang ◽  
Alex Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Lean Mass ◽  
Muscle Function ◽  
Muscle Wasting ◽  
Nephropathic Cystinosis ◽  
Mass Content ◽  
Aberrant Expression ◽  
Fiber Size ◽  
Tissue Browning

ABSTRACTBackgroundCtns−/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Inflammatory cytokines such as IL-1 trigger inflammatory cascades and play an important role in the pathogenesis of cachexia. Anakinra is an FDA-approved IL-1 receptor antagonist that blocks IL-1 signaling and may provide targeted novel therapy.MethodsCtns−/− mice were bred to Il6−/− and Il1β−/− mice. Ctns−/− mice and wild type control were treated with anakinra (2.5 mg.kg.day, IP) or saline as vehicle for 6 weeks. We quantitated total fat mass and studied expression of molecules regulating adipose tissue browning. We measured gastrocnemius weight, total lean mass content, muscle function (grip strength and rotarod activity), muscle fiber size, muscle fatty infiltration and expression of molecules regulating muscle metabolism. We also evaluated the effects of anakinra on the muscle transcriptome.ResultsIl-1β deficiency or treatment with anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function in Ctns−/− mice. Anakinra also diminished molecular perturbations of energy homeostasis in adipose tissue and muscle, specifically, aberrant expression of beige adipose cell biomarkers (UCP-1, CD137, Tmem26 and Tbx1) and molecules implicated in adipocyte tissue browning (Cox2/Pgf2α, Tlr2, Myd88 and Traf6) in inguinal white adipose tissue in Ctns−/− mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns−/− mice. This was accompanied by correction of the increased muscle wasting signaling pathways (increased protein content of ERK1/2, JNK, p38 MAPK and NF-κB p65 and gene expression of Atrogin-1 and Myostatin) and the decreased myogenesis process (decreased gene expression of MyoD and Myogenin) in gastrocnemius of Ctns−/− mice. Finally, anakinra normalized or attenuated 12 of those top 20 differentially expressed muscle genes in Ctns−/− mice.ConclusionsAnakinra attenuates adipose tissue browning and muscle wasting in Ctns−/− mice. IL-1 receptor blockade may represent a novel targeted treatment for cachexia in patients with infantile nephropathic cystinosis.

scholarly journals Differential Effects of 25-Hydroxyvitamin D3 versus 1α 25-Dihydroxyvitamin D3 on Adipose Tissue Browning in CKD-Associated Cachexia

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3382
Author(s):  
Robert H. Mak ◽  
Uwe Querfeld ◽  
Alex Gonzalez ◽  
Sujana Gunta ◽  
Wai W. Cheung
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Muscle Wasting ◽  
Resting Metabolic Rate ◽  
Dihydroxyvitamin D3 ◽  
Differential Effects ◽  
Muscle Fibrosis ◽  
Tissue Browning

Patients with chronic kidney disease (CKD) often have low serum concentrations of 25(OH)D3 and 1,25(OH)2D3. We investigated the differential effects of 25(OH)D3 versus 1,25(OH)2D3 repletion in mice with surgically induced CKD. Intraperitoneal supplementation of 25(OH)D3 (75 μg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) for 6 weeks normalized serum 25(OH)D3 or 1,25(OH)2D3 concentrations in CKD mice, respectively. Repletion of 25(OH)D3 normalized appetite, significantly improved weight gain, increased fat and lean mass content and in vivo muscle function, as well as attenuated elevated resting metabolic rate relative to repletion of 1,25(OH)2D3 in CKD mice. Repletion of 25(OH)D3 in CKD mice attenuated adipose tissue browning as well as ameliorated perturbations of energy homeostasis in adipose tissue and skeletal muscle, whereas repletion of 1,25(OH)2D3 did not. Significant improvement of muscle fiber size and normalization of fat infiltration of gastrocnemius was apparent with repletion of 25(OH)D3 but not with 1,25(OH)2D3 in CKD mice. This was accompanied by attenuation of the aberrant gene expression of muscle mass regulatory signaling, molecular pathways related to muscle fibrosis as well as muscle expression profile associated with skeletal muscle wasting in CKD mice. Our findings provide evidence that repletion of 25(OH)D3 exerts metabolic advantages over repletion of 1,25(OH)2D3 by attenuating adipose tissue browning and muscle wasting in CKD mice.

Insulin Sensitizing Effects of Vitamin D Mediated through Reduced Adipose Tissue Inflammation and Fibrosis

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 39-OR
Author(s):  
ERIC LONTCHI-YIMAGOU ◽  
SONA KANG ◽  
KEHAO ZHANG ◽  
AKANKASHA GOYAL ◽  
JEE YOUNG YOU ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

1944-P: CREBZF Acetylation at Lys126 Couples Glucose to White Adipose Tissue Browning

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1944-P
Author(s):  
AOYUAN CUI ◽  
WEITONG SU ◽  
YAQIAN XUE ◽  
ZHENGSHUAI LIU ◽  
FENGGUANG MA ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Tissue Browning

Adipose Tissue Remodeling by Prolonged Administration of High Dose of Vitamin D3 in Rats Treated to Prevent Sarcopenia

2017 ◽  
Vol 68 (9) ◽  
pp. 2139-2143 ◽  
Author(s):  
Alin Constantin Pinzariu ◽  
Sorin Aurelian Pasca ◽  
Allia Sindilar ◽  
Cristian Drochioi ◽  
Mihail Balan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D3 ◽  
Term Treatment ◽  
High Dose ◽  
Omental Adipose Tissue ◽  
Long Term Treatment ◽  
Male Wistar Rats ◽  
Adipose Tissue Remodeling ◽  
Visceral Adipose

To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.

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