Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.

White, Roger; Damm, D; Hancock, N.; Rosen, Barry; Lowell, Brad B.; Usher, Patricia; Flier, Jeffrey S.; Spiegelman, Bruce M.

doi:10.1016/s0021-9258(19)50409-4

Cited by 332 publications

(68 citation statements)

References 22 publications

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“…ASP is a 76 amino acid fragment of the third component of complement (C3) and is produced by the interaction of C3, factor B, and adipsin (3). These three proteins are synthesized and secreted by both murine (5) and human adipocytes (4,6) in a differentiation-dependent manner (7). The carboxy terminal arginine of the initial product, C3a, is cleaved by carboxypeptidase to generate C3adesArg.…”

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confidence: 99%

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period

Saleh

Summers

Cianflone

et al. 1998

Journal of Lipid Research

128

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The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) with maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominant until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT ( r ϭ 0.566, P Ͻ 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.

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confidence: 99%

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period

Saleh

Summers

Cianflone

et al. 1998

Journal of Lipid Research

128

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“…Adipsin, also called Complement Factor D ( Rosen et al, 1989 ; White et al, 1992 ), is an established activator of Complement Component 3 (C3), the central player of the complement system ( Xu et al, 2001 ; Sahu and Lambris, 2001 ). C3 deficiency has been shown to protect mice from ovariectomy-induced bone loss ( MacKay et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Among them, Adipsin was the first adipocyte-secreted protein discovered in 1987 ( Cook et al, 1987 ). It has since been identified as Complement Factor D (CFD) ( Rosen et al, 1989 ; White et al, 1992 ), a rate-limiting factor in the alternative pathway of the complement system ( Xu et al, 2001 ). While many components of the complement system are produced by hepatocytes, macrophages, or endothelial cells, Adipsin is produced nearly exclusively by adipocytes ( Choy et al, 1992 ) through the activation of PPARγ ( Tontonoz et al, 1994 ).…”

Section: Introductionmentioning

confidence: 99%

Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells

Aaron

Kraakman

Zhou

et al. 2021

eLife

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Background:Marrow adipose tissue (MAT) has been shown to be vital for regulating metabolism and maintaining skeletal homeostasis in the bone marrow (BM) niche. As a reflection of BM remodeling, MAT is highly responsive to nutrient fluctuations, hormonal changes, and metabolic disturbances such as obesity and diabetes mellitus. Expansion of MAT has also been strongly associated with bone loss in mice and humans. However, the regulation of BM plasticity remains poorly understood, as does the mechanism that links changes in marrow adiposity with bone remodeling.Methods:We studied deletion of Adipsin, and its downstream effector, C3, in C57BL/6 mice as well as the bone-protected PPARγ constitutive deacetylation 2KR mice to assess BM plasticity. The mice were challenged with thiazolidinedione treatment, calorie restriction, or aging to induce bone loss and MAT expansion. Analysis of bone mineral density and marrow adiposity was performed using a μCT scanner and by RNA analysis to assess adipocyte and osteoblast markers. For in vitro studies, primary bone marrow stromal cells were isolated and subjected to osteoblastogenic or adipogenic differentiation or chemical treatment followed by morphological and molecular analyses. Clinical data was obtained from samples of a previous clinical trial of fasting and high-calorie diet in healthy human volunteers.Results:We show that Adipsin is the most upregulated adipokine during MAT expansion in mice and humans in a PPARγ acetylation-dependent manner. Genetic ablation of Adipsin in mice specifically inhibited MAT expansion but not peripheral adipose depots, and improved bone mass during calorie restriction, thiazolidinedione treatment, and aging. These effects were mediated through its downstream effector, complement component C3, to prime common progenitor cells toward adipogenesis rather than osteoblastogenesis through inhibiting Wnt/β-catenin signaling.Conclusions:Adipsin promotes new adipocyte formation and affects skeletal remodeling in the BM niche. Our study reveals a novel mechanism whereby the BM sustains its own plasticity through paracrine and endocrine actions of a unique adipokine.Funding:This work was supported by the National Institutes of Health T32DK007328 (NA), F31DK124926 (NA), R01DK121140 (JCL), R01AR068970 (BZ), R01AR071463 (BZ), R01DK112943 (LQ), R24DK092759 (CJR), and P01HL087123 (LQ).

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Section: Introductionmentioning

confidence: 99%

“…Complement factor D (FD), also termed adipsin, is a serine protease with a crucial role in the activation of the AP of the complement system [ 8 , 9 ]. FD is secreted by several tissues and cell types, although the major source in humans is mature adipocytes and macrophages in adipose tissue [ 8 , 9 , 10 ]. Given the connection of FD with adipose tissue and complement system activation, it could be considered a central player in the pathogenesis of BSS, as previously suggested by other authors [ 4 , 5 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)

Corvillo

González-Sánchez

López‐Lera

et al. 2021

IJMS

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Complement overactivation has been reported in most patients with Barraquer–Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient’s adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.

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Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.

Cited by 332 publications

References 22 publications

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period

Adipsin promotes bone marrow adiposity by priming mesenchymal stem cells

Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer–Simons syndrome)

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