C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight

Byerly, Mardi S.; Petersen, P. H.; Ramamurthy, Santosh; Seldin, Marcus M.; Lei, Xia; Provost, Elayne; Wei, Zhikui; Ronnett, Gabriele V.; Wong, G. William

doi:10.1074/jbc.m113.506956

Cited by 61 publications

(67 citation statements)

References 75 publications

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“…Cow HPs are part of the C1q protein family (Kishore et al, 2004) and consist of over 30 members, all of which possess the signature C1q domain at the C-terminus. Several conserved members of this family, such as adiponectin and C1q/TNF-related proteins are involved in modulating food intake (Byerly et al, 2014;Byerly et al, 2013a;Kubota et al, 2007;Qi et al, 2004) and energy metabolism (Berg et al, 2001;Peterson et al, 2012;Peterson et al, 2013;Peterson et al, 2010;Seldin et al, 2012;Wei et al, 2014;Wei et al, 2012b;Wei et al, 2011;Wei et al, 2013;Wong et al, 2009;Wong et al, 2008;Yamauchi et al, 2002). Thus, in mice, the functional homolog of cow HPs may be subsumed by other related C1q family members.…”

Section: Discussionmentioning

confidence: 99%

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

Seldin

Byerly

Petersen

et al. 2014

Journal of Experimental Biology

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Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related nonhibernating tree squirrels, leading to the suggestion that hibernationspecific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver-brain circuit may couple seasonal changes in the environment to alterations in physiology.

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Section: Discussionmentioning

confidence: 99%

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

Seldin

Byerly

Petersen

et al. 2014

Journal of Experimental Biology

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“…In 2004, Wong et al characterized a novel family of adipose tissue-derived cytokines, collectively called adipokines, referred to as Complement C 1q T umor necrosis factor- R elated P roteins (CTRPs) (76), like adiponectin and tumor necrosis factor (TNF) these CTRPs all contain a C1q globular domain and are characterized together as the C1q/TNF superfamily (62). To date, this superfamily has been documented to have a wide range and opposing effects on metabolism, food intake, inflammation, tumor metastasis, apoptosis, vascular disorders, ischemic injury, and even sexual reproduction (7, 8, 25, 29, 30, 49, 51, 57, 62, 64, 68, 69, 74-76, 81, 84, 89). The purpose of this review is to carefully summarize the research that has been accomplished on one of these proteins, CTRP3.…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

Liu

Wright

Peterson

2017

Comprehensive Physiology

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As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines. Efforts to identify such metabolic regulators have led to the discovery of a family of secreted proteins, designated as C1q tumor necrosis factor (TNF)-related proteins (CTRPs). The CTRP proteins, adiponectin, TNF-alpha, as well as other proteins with the distinct C1q domain are collectively grouped together as the C1q/TNF superfamily. Reflecting profound biological potency, the initial characterization of these adipose tissue-derived CTRP factors finds wide-ranging effects upon metabolism, inflammation, and survival-signaling in multiple tissue types. CTRP3 (also known as CORS26, cartducin, or cartonectin) is a unique member of this adipokine family. In this review we provide a comprehensive overview of the research concerning the expression, regulation, and physiological function of CTRP3.

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“…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).…”

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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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C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight

Cited by 61 publications

References 75 publications

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

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

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