The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway

Otani, Masataka; Kogo, Mikihiko; Furukawa, Souhei; Wakisaka, Satoshi; Maeda, Takashi

doi:10.1016/j.cyto.2012.01.018

Cited by 30 publications

(30 citation statements)

References 42 publications

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“…Interestingly, overexpressing CTRP3 in mice also promotes phosphate-induced vascular smooth muscle cell calcification (73). Although the physiological relevance is unclear, multiple in vitro studies also imply a role for CTRP3 in regulating adipocyte (27,28), leydig (37), chrondocyte (32), osteocyte (2), endothelial (1), fibroblast (30), and cartilage (70) cell function.…”

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confidence: 99%

CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

Wolf

Lei

Zhi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Wolf RM, Lei X, Yang Z, Nyandjo M, Tan SY, Wong GW. CTRP3 deficiency reduces liver size and alters IL-6 and TGF␤ levels in obese mice. Am J Physiol Endocrinol Metab 310: E332-E345, 2016. First published December 15, 2015; doi:10.1152/ajpendo.00248.2015.-C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD-or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGF␤1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. adipokine; C1q/tumor necrosis factor-related protein; C1q/tumor necrosis factor; fatty liver; obesity; diabetes THE C1Q/TNF-RELATED PROTEIN (CTRP) family comprises 15 secreted plasma proteins of the C1q family, the first seven of which were identified initially on the basis of sequence homology to the globular C1q domain of adiponectin (66); additional members were subsequently described (6, 43, 49, 59 -61, 64, 65). Recent functional studies demonstrated important and distinct roles for CTRPs in regulating glucose and/or lipid metabolism in the peripheral tissues (38 -42, 57-60) as well as having a central role in modulating food intake (6, 7) and adipocyte differentiation in culture (61). Unlike adiponectin, whose expression is restricted to adipocytes (47), CTRP family members are much more widely expressed (65, 66); all are conserved throughout vertebrate evolution (50).Multiple in vitro and in vivo approaches have been used to elucidate the biological function of one member, CTRP3, a secreted plasma protein whose circulating levels ...

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confidence: 99%

CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

Wolf

Lei

Zhi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…MEK1/2 inhibitor U0126 was purchased from Calbiochem (San Diego, CA, USA). Recombinant full-length mouse CTRP3, containing a C-terminal FLAG tag epitope, was produced in mammalian cells as described previously [21]. Recombinant human TGF-b3 was purchased from PeproTech (Rocky Hill, NJ, USA).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

“…To analyze the distribution of CTRP3 in skeletal muscle tissues of 4-week-old mice (C57BL/6) and sagittal sections of mouse embryos (E12.5-E13.5), immunohistochemistry was performed as described previously [21]. The tissue samples were fixed in 4 % paraformaldehyde and embedded in paraffin.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Fetal and adult human Northern Lights TM Multiple mRNA Blots (GIBCO BRL, Grand Island, NY, USA) were hybridized with a PCR-amplified cDNA fragment of human CTRP3 [21] labeled with [ 32 P]dCTP by the random priming method. Pre-hybridization, hybridization, washing, and autoradiography were performed as described previously [11].…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…To determine the growth-stimulating effect of CTRP3 on C2C12 myoblasts, the bromodeoxyuridine (BrdU) assay was performed as described previously [21]. Briefly, C2C12 myoblasts were seeded at a density of 5 9 10 3 cells/well in 96-well plates and grown for 24 h. Cells were then washed and the medium was replaced with DMEM without serum for 24 h. Subsequently, various concentrations of recombinant CTRP3 were added to the medium, and cells were incubated for 24 h and labeled with BrdU during the last 3 h of incubation.…”

Section: Measurement Of Dna Synthesismentioning

confidence: 99%

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A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation

et al. 2015

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Several hormones and growth factors, including adipokines, play important roles during muscle development and regeneration. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 is a novel adipokine previously reported to reduce glucose output in hepatocytes and lower glucose levels in mice models. In the present study, we provide the first evidence for a physiological role of the CTRP3 in myogenesis using C2C12 myoblasts. CTRP3 was expressed in developing skeletal muscle tissues, and the expression level of CTRP3 was increased during myogenic differentiation of C2C12 cells. Recombinant CTRP3 (rCTRP3) promoted the proliferation of undifferentiated C2C12 myoblasts and this response required activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In contrary, rCTRP3 inhibited myogenic differentiation and fusion of C2C12 cells by suppressing the expression of myogenic marker genes (myogenin and myosin heavy chain). CTRP3 mRNA expression was increased in C2C12 myoblasts treated with transforming growth factor-β3 (TGF-β3), suggesting that TGF-β3 is one of the extracellular factors regulating CTRP3 expression during myogenesis. These results indicate a novel physiological role for CTRP3 during skeletal myogenesis.

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C1q/TNF‐related protein 3 expression and effects on adipocyte differentiation of 3T3‐L1 cells

Nishimoto

Yamamoto

Furukawa

et al. 2016

Cell Biology International

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Adipose tissue-derived adipokines influence a number of organs critical for energy homeostasis and metabolism. One of the most extensively studied adipokines is adiponectin, which exerts anti-diabetic, anti-inflammatory, and anti-atherogenic functions on various cell types. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 reduces hepatic triglyceride levels in diet-induced obese (DIO) mice. However, the physiological role of CTRP3 in adipocytes is largely unknown. In the course of our investigation of expression profiles of CTRPs during adipocyte differentiation, we found that CTRP3 expression pattern is different from that previously reported. Therefore, we examined the effect of CTRP3 on adipogenesis using 3T3-L1 cells. The expression level of CTRP3 was markedly decreased during the differentiation of 3T3-L1 cells. Recombinant CTRP3 (rCTRP3) treatment significantly reduced intracellular lipid content and decreased expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, and fatty acid binding protein 4 (FABP4) in 3T3-L1 cells. Furthermore, rCTRP3 induced the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and Akt in differentiated 3T3-L1 adipocytes. These results suggest that CTRP3 may negatively regulate lipid metabolism during adipocyte differentiation.

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The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway

Cited by 30 publications

References 42 publications

CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

A novel adipokine C1q/TNF-related protein 3 is expressed in developing skeletal muscle and controls myoblast proliferation and differentiation

C1q/TNF‐related protein 3 expression and effects on adipocyte differentiation of 3T3‐L1 cells

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