Serum Haptoglobin: A Novel Marker of Adiposity in Humans

Chiellini, Chiara; Santini, Ferruccio; Marsili, Alessandro; Berti, Piero; Bertacca, A; Pelosini, Caterina; Scartabelli, Giovanna; Pardini, E.; López‐Soriano, Joaquín; Centoni, Roberta; Ciccarone, Annamaria; Benzi, Luca; Vitti, Paolo; Prato, Stefano Del; Pinchera, Aldo; Maffei, Margherita

doi:10.1210/jc.2003-031965

Cited by 105 publications

(85 citation statements)

References 29 publications

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“…However, it may be that there is a causal link between these clinically related phenotypes. For example, the haptoglobin gene is expressed in white adipose tissue and circulating haptoglobin is positively correlated to fat mass in humans (17). Serum haptoglobin responses to ovalbumin were greater in the fatter female than in male offspring.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

Sinclair

Allegrucci

Singh

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

701

543

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A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B12 and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult healthrelated phenotypes. E vidence from both epidemiological studies in humans and direct intervention studies in animals indicates that altering key developmental processes in utero can predispose offspring to many late-onset diseases such as dyslipidemia, type II diabetes, and heart disease (1, 2). In this regard, the effects of gross nutrient or protein deficiencies in maternal diet during pregnancy are well documented (3), although little is known about the effects of specific nutrients or the timing and mechanistic basis of nutrient programming (4). Here we investigated the effects of restricting the supply of specific B group vitamins (i.e., vitamin B 12 and folate) and sulfur amino acids (in particular, methionine) from the diet of adult female sheep from 8 weeks preceding until 6 days after conception, within physiological ranges encountered in both sheep (5) and humans (i.e., within the 5th and 95th percentiles) (6, 7). These micronutrients are important intermediates and/or have specific regulatory functions in the linked methionine-folate cycles (5, 7). In rodents, maternal supraphysiological methyl group supply and a low-protein diet (50% control) offered throughout pregnancy altered DNA methylation of candidate genes (agouti, glucocorticoid receptor, and peroxisomal proliferator-activated receptor-␣) (8, 9), but the extent of methylation change in these or more clinically relevant diets is not known. Gametes and preimplantation emb...

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Section: Discussionmentioning

confidence: 99%

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

Sinclair

Allegrucci

Singh

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

701

543

View full text Add to dashboard Cite

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“…Indeed, it has been shown that the 4 Some of these are recognised as acute-phase proteins of inflammation (e.g. IL6, 5 C-reactive protein [CRP] 6 and haptoglobin 7,8 ). Furthermore, we have observed that different isoforms of the serum amyloid A (SAA) protein, usually known to be produced by the liver, can also be produced by the WAT.…”

Section: Origin Of Chronic Inflammation In Obesity and Contribution Omentioning

confidence: 99%

Review article: Is obesity an inflammatory illness? Role of low‐grade inflammation and macrophage infiltration in human white adipose tissue

Cancello

Clément²

2006

BJOG

378

278

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There are at least two scientific evidences of human obesity as a chronic inflammatory illness: first, the well-described moderate increase of inflammatory factors in the circulation in obese subjects, and second, the recent identification of macrophage cells infiltrating the white adipose tissue (WAT). These observations led to a revision of the physiopathology of obesity and its co-morbidities. It has been suggested that the 'low-grade' inflammatory state associates with metabolic and cardiovascular complications of obesity. Weight loss is able to improve this inflammatory state by both significantly decreasing circulating inflammatory molecules and macrophage cell infiltration in WAT depots. However, the mechanisms of WAT macrophage recruitment into the adipose tissue and their role in obesity complications have not been defined. This review aims to point out the knowledge on inflammatory cytokines associated with obesity and focuses on macrophage infiltration in human WAT, discussing their recruitment and role. The interactions of macrophages with adipocytes will certainly be the subject of intense investigations in the future.

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“…Haptoglobin and serum amyloid protein A, both proteins involved in the acute-phase response to inflammation, have also been shown to circulate in higher concentrations in people with more body fat. [74][75][76] The sample sizes in these studies are smaller and typically not population-based, but across these studies the data are consistent. In an interesting study 63 involving identical twins discordant for obesity (the average difference in body weight between twin pairs was 18 kg), levels of TNF-α and soluble TNF-α receptor 2 (sTNFR2) were higher in obese than in lean twins, which suggests that obesity rather than other genetic factors is a major determinant of these inflammatory markers.…”

Section: Role Of Adiposity and Weight Loss In Regulating Inflammationmentioning

confidence: 99%

Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training

Nicklas¹

2005

Canadian Medical Association Journal

212

143

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Review SynthèseT he biologic cascade of events that form the body's natural defenses against injury or infection is a vital part of the immune system. Ordinarily, this process is an acute response resulting in rapid, major increases in inflammatory mediators released into the circulation. 1,2 In healthy, lean, non-elderly people, for example, blood concentrations of the acute-phase reactant C-reactive protein (CRP), which are normally less than 2 mg/L in men 3 and less than 2.5 mg/L in women, 4 can increase more than 1000-fold in response to infection or trauma. 2,5,6 Typically, a CRP value of 10 mg/L or more is considered indicative of clinically significant inflammation. 7 However, recent evidence indicates that persistent elevations in circulating markers of inflammation, even when within the clinically normal range, are risk factors for cardiovascular disease in both middle-aged [8][9][10][11][12][13] and older [14][15][16][17][18][19] people. Recently, the US Centers for Disease Control and Prevention and the American Heart Association have stated that people with CRP values in the upper tertile of the adult population (> 3.0 mg/L) have a risk of cardiovascular disease that is double that of people whose CRP concentrations are less than 1.0 mg/L. 20In addition to CRP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), along with several other acutephase reactant proteins, cytokines and cytokine-soluble receptors, are strongly associated with increased risk for several chronic diseases, including cardiovascular disease, 12,17,21,22 diabetes mellitus 23,24 and disability. 25,26 IL-6 and TNF-α are both stimulators of CRP release from hepatocytes.27,28 It is not yet known which of these factors might be the most robust indicator of underlying inflammation, or whether the effects of these biomarkers are additive for risk prediction.As illustrated in Figure 1, behavioural factors are associated with chronic, low-grade states of inflammation (as measured by slightly elevated inflammatory biomarkers), and therefore with the several chronic diseases that are associated with inflammatory states. Since the risk estimates associated with elevated inflammation appear to be linear (e.g., the CRP category cut-offs for assessment of cardiovascular disease risk 20 are low risk < 1.0 mg/L, medium risk 1.0-3.0 mg/L and high risk > 3.0 mg/L), behavioural interventions that produce even slight reductions in inflammation may have clinically significant benefits. A few pharmacologic interventions such as use of angiotensin-converting-enzyme inhibitors and statins decrease inflammation, as evidenced by lowered CRP concentrations in prospective clinical trials. [29][30][31][32] Moreover, there are very promising data suggesting that decreasing body weight and increasing physical activity are just as effective as medication for reducing overall inflammation. The published effects of behavioural interventions involving weight loss and exercise training on inflammatory markers are reviewed here. Role of adiposity and weigh...

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Serum Haptoglobin: A Novel Marker of Adiposity in Humans

Cited by 105 publications

References 29 publications

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

Review article: Is obesity an inflammatory illness? Role of low‐grade inflammation and macrophage infiltration in human white adipose tissue

Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training

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