Lower Circulating C1q/TNF-Related Protein-3 (CTRP3) Levels Are Associated with Obesity: A Cross-Sectional Study

Wolf, Risa M.; Steele, Kimberley E.; Peterson, Leigh; Magnuson, Thomas; Schweitzer, Michael; Wong, G. William

doi:10.1371/journal.pone.0133955

Cited by 71 publications

(69 citation statements)

References 39 publications

(54 reference statements)

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“…In light of the myriad functions demonstrated for CTRP3 based on recombinant protein supplementation and overexpression in rodents, our current loss-of-function studies using Ctrp3-KO mice help provide critical insights into the functional significance of this secreted plasma protein that exhibits reduced circulating levels in rodent models of obesity and diabetes (29,42) as well as in obese and diabetic humans (3,9,63,71). Based on our previous studies using recombinant protein infusion and transgenic overexpression in mice (40,42), we expected the Ctrp3-KO mice to exhibit impaired energy balance.…”

Section: Discussionmentioning

confidence: 99%

“…Functional insights gained from multiple rodent models have prompted recent investigations of CTRP3 plasma levels in humans; however, conflicting results have been reported for its association with diabetes and the metabolic syndrome (3,8,63,71). The first study showed elevated CTRP3 levels in patients with type 2 diabetes (8), whereas subsequent studies reported lower levels of CTRP3 in individuals with metabolic syndrome (71), newly diagnosed patients with type 2 diabetes (3), obesity (63), or obese patients with hypertension and insulin resistance (9). Furthermore, women with polycystic ovarian syndrome were also found to have lower circulating CTRP3 levels compared with their matched controls, and metformin treatment was found to increase CTRP3 serum levels (54).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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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“…AMPKα is activated by adiponectin and the novel adipokine C1q/tumour necrosis factor-related protein-3 (CTRP3) which provides protection from hyperglycemia induced oxidative stress, inflammation, and apoptosis in vitro 112 . Both CTRP3 and adiponectin belong to the C1q/TNF superfamily CTRP3 and suppress hepatic gluconeogenesis 113 and are decreased with obesity 114 . Activation of AMPK by metformin restored ROS-impaired autophagy in senescent cells 115 .…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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“…Their plasma levels vary with the genetic background, age, gender, and metabolic states. In terms of CTRPs sexually dimorphic patterns, female mice express higher levels of CTRP13, CTRP11, CTRP9, CTRP5, and CTRP3 compared to male animals/humans [1][2][3][4][5] . The exact mechanism for these differences is still unclear.…”

Section: What Are Ctrps?mentioning

confidence: 99%

“…The distribution of CTRPs levels Oligomer varies and is influenced by metabolic hormones, significant signaling and inflammator y states, meanwhile, they can exist in autocrine, paracrine, and endocrine manners that influence the individual susceptibility to the disease and therefore, it provides the possibility that they timely reflect the processing of insulin resistance, obesity, and type 2 diabetes. Accumulated studies reveal that circulating levels of CTRP3, CTRP6, CTRP7, CTRP9, CTRP12, and CTRP15 are reduced in diet-induced diabetes or obese mice or humans [4,5,[7][8][9] . CTRP1 and CTRP5 concentrations are higher in obese and diabetic rodents [10] .…”

Section: Ctrps In Circulationmentioning

confidence: 99%

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

Wang¹,

Zhao²,

Liu³

et al. 2017

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How to cite this article: Wang YJ, Zhao JL, Lau WB, Liu J, Guo R, Ma XL. Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system. Vessel Plus 2017;1:202-12.Increasing evidence indicates that adipose tissue-originated cytokines mediate communication between obesity-related exogenous molecules and the molecular events that initiate the metabolic syndrome and the inflammatory responses in the cardiovascular system (CVS). Adipose tissue-derived cytokines including the C1q/tumor necrosis factor-related proteins (CTRPs), a 15-member family of novel adipokines, has attracted much interest due to its metabolic regulatory and anti-inflammatory effect and appear to play a pathophysiological role in metabolism and immunity. To date, 15 members of CTRP family have been identified and they also play a role in the CVS, especially as potent biomarkers or therapeutic targets for modulating metabolic or inflammatory functions. Therefore, this review will focus on the characteristics of CTRPs that influence cardiovascular function and on the potential of CTRPs as biomarkers and therapeutic targets. Key words:Adipose tissue-derived cytokines, adipokines, C1q/tumor necrosis factor-related proteins, metabolism, cardiovascular system, biomarker, therapeutic target ABSTRACTArticle history:

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Lower Circulating C1q/TNF-Related Protein-3 (CTRP3) Levels Are Associated with Obesity: A Cross-Sectional Study

Cited by 71 publications

References 39 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

Macrophage functions in lean and obese adipose tissue

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

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