Late‐onset renal hypertrophy and dysfunction in mice lacking CTRP1

Rodriguez, Susana; Little, Hannah C.; Daneshpajouhnejad, Parnaz; Shepard, Blythe D.; Tan, Stephen; Wolfe, Andrew; Cheema, Muhammad Umar; Jandu, Sandeep; Woodward, Owen M.; Talbot, C. Conover; Berkowitz, Dan E.; Rosenberg, Avi Z.; Pluznick, Jennifer L.; Wong, G. William

doi:10.1096/fj.201900558rr

Cited by 8 publications

(5 citation statements)

References 84 publications

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“…4,5 Within this family, there is a subgroup of 15 proteins referred to as the C1q/ TNF-related proteins (CTRP1-15), 6 which we have initially identified based on shared sequence homology to the insulin-sensitizing hormone, adiponectin. 7,8 Multiple approaches-involving recombinant protein infusion, transgenic overexpression, and knockout mouse modelshave provided critical in vivo evidence for CTRPs in regulating diverse aspects of glucose and lipid metabolism, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] obesity-linked low-grade inflammation, 10,27 as well as other diverse functions in the heart and vasculature, [28][29][30][31][32][33][34] kidney, [35][36][37] muscle and tendon, 38,39 bone, 40 immune system, [41][42][43][44] and the central nervous system. [45][46][47]…”

Section: Introductionmentioning

confidence: 99%

CTRP11 contributes modestly to systemic metabolism and energy balance

Sarver

Carreno

et al. 2022

The FASEB Journal

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C1q/TNF‐related proteins (CTRP1‐15) constitute a conserved group of secreted proteins of the C1q family with diverse functions. In vitro studies have shown that CTRP11/C1QL4 can inhibit adipogenesis, antagonize myoblast fusion, and promote testosterone synthesis and secretion. Whether CTRP11 is required for these processes in vivo remains unknown. Here, we show that knockout (KO) mice lacking CTRP11 have normal skeletal muscle mass and function, and testosterone level, suggesting that CTRP11 is dispensable for skeletal muscle development and testosterone production. We focused our analysis on whether this nutrient‐responsive secreted protein plays a role in controlling sugar and fat metabolism. At baseline when mice are fed a standard chow, CTRP11 deficiency affects metabolic parameters in a sexually dimorphic manner. Only Ctrp11‐KO female mice have significantly higher fasting serum ketones and reduced physical activity. In the refeeding phase following food withdrawal, Ctrp11‐KO female mice have reduced food intake and increased metabolic rate and energy expenditure, highlighting CTRP11’s role in fasting–refeeding response. When challenged with a high‐fat diet to induce obesity and metabolic dysfunction, CTRP11 deficiency modestly exacerbates obesity‐induced glucose intolerance, with more pronounced effects seen in Ctrp11‐KO male mice. Switching to a low‐fat diet after obesity induction results in greater fat loss in wild type relative to KO male mice, suggesting impaired response to obesity reversal and reduced metabolic flexibility in the absence of CTRP11. Collectively, our data provide genetic evidence for novel sex‐dependent metabolic regulation by CTRP11, but note the overall modest contribution of CTRP11 to systemic energy homeostasis.

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Section: Introductionmentioning

confidence: 99%

CTRP11 contributes modestly to systemic metabolism and energy balance

Sarver

Carreno

et al. 2022

The FASEB Journal

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“…CTRP1-KO 1 Defective blood pressure homeostasis [63] CTRP1-KO Low-fat diet: insulin resistance and hepatic steatosis High-fat diet: reduced body weight, adiposity and hepatic steatosis [64] CTRP1-tg 2 Reduced DOX-induced cardiac injury [65] Adeno-CTRP1 CTRP1-KO Inhibition of neointimal thickening [66] Recombinant CTRP1 in non-human primates Antiplatelet thrombotic activity [67] CTRP1-KO Increased myocardial infarct size, cardiomyocyte apoptosis, and inflammatory gene expression after I/R [59] CTRP1-KO Increase in kidney weight, glomerular hypertrophy, and elevated blood pressure in aged male [68] CTRP2 CTRP2-tg Improved insulin tolerance [69] CTRP2-KO Up-regulation of lipolytic enzymes [70] Injection of recombinant CTRP2 Reduced infarct size and improved blood flow after I/R [58] CTRP3 ApoE−/− 3 Reduced CTRP3 expression [71] Overexpression…”

Section: Ctrp1mentioning

confidence: 99%

Complement 1q/Tumor Necrosis Factor-Related Proteins (CTRPs): Structure, Receptors and Signaling

et al. 2023

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Adiponectin and the other 15 members of the complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) family are secreted proteins composed of an N-terminal variable domain followed by a stalk region and a characteristic C-terminal trimerizing globular C1q (gC1q) domain originally identified in the subunits of the complement protein C1q. We performed a basic PubMed literature search for articles mentioning the various CTRPs or their receptors in the abstract or title. In this narrative review, we briefly summarize the biology of CTRPs and focus then on the structure, receptors and major signaling pathways of CTRPs. Analyses of CTRP knockout mice and CTRP transgenic mice gave overwhelming evidence for the relevance of the anti-inflammatory and insulin-sensitizing effects of CTRPs in autoimmune diseases, obesity, atherosclerosis and cardiac dysfunction. CTRPs form homo- and heterotypic trimers and oligomers which can have different activities. The receptors of some CTRPs are unknown and some receptors are redundantly targeted by several CTRPs. The way in which CTRPs activate their receptors to trigger downstream signaling pathways is largely unknown. CTRPs and their receptors are considered as promising therapeutic targets but their translational usage is still hampered by the limited knowledge of CTRP redundancy and CTRP signal transduction.

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“…CTRPs control various aspects of glucose and lipid metabolism by either directly acting on metabolic tissues (e.g., liver, adipose tissue, skeletal muscle) or indirectly via their modulatory roles on immune cells and inflammation [ 15 , 30 ]. Additional functions of CTRPs have also been established in the cardiovascular system [ [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] ], kidney [ 43 , 44 ], gut [ 45 ], eye [ 46 , 47 ], musculoskeletal system [ [48] , [49] , [50] ], and brain [ [51] , [52] , [53] ].…”

Section: Introductionmentioning

confidence: 99%

CTRP13 ablation improves systemic glucose and lipid metabolism

Chen,

Sarver,

Saqib

et al. 2023

Molecular Metabolism

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Late‐onset renal hypertrophy and dysfunction in mice lacking CTRP1

Cited by 8 publications

References 84 publications

CTRP11 contributes modestly to systemic metabolism and energy balance

CTRP11 contributes modestly to systemic metabolism and energy balance

Complement 1q/Tumor Necrosis Factor-Related Proteins (CTRPs): Structure, Receptors and Signaling

CTRP13 ablation improves systemic glucose and lipid metabolism

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