Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFα

Abstract

Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals. Hp is a glycoprotein induced by a number of cytokines, LPS (Lipopolysaccharide), and more generally by inflammation. A significant upregulation of WAT Hp expression was also evident in several experimental obese models including the yellow agouti (/) A(y), ob/ob and goldthioglucose-treated mice (10-, 8-, and 7-fold, respectively). To identify the potential signals for an increase in Hp expression in obesity, we examined leptin and TNFalpha in vivo. Wild type animals treated with recombinant leptin did not show any alteration in WAT Hp expression compared to controls that were food restricted to the level of intake of the treated animals. On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue. Finally, a significant downregulation of WAT Hp mRNA was observed in ob/ob mice deficient in TNFalpha function, when compared to the ob/ob controls. These results demonstrate that haptoglobin expression in WAT is increased in obesity in rodents and TNFalpha is an important signal for this regulation.

Haptoglobin release by human adipose tissue in primary culture

“…A genomic approach resulted in a similar finding, because haptoglobin mRNA was found to be significantly upregulated in the adipose tissue of obese rodents (2,3). Furthermore, haptoglobin is present at increased levels in the blood of obese humans (4,5).…”

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

“…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.…”

Haptoglobin Phenotype and Gestational Diabetes

“…Because BMI correlates positively with oxidative stress (31), this finding supports the suggestion that differences in the antioxidative function of Hp phenotypes contribute to the development of GDM. Elevated serum levels of Hp found in GDM (Table 1) may reflect the higher BMI present in women with GDM, leading to increased expression of Hp in fat tissue (1). In fact, we observed a significant correlation between BMI and Hp levels, and no significant risk could be attributed to Hp levels in a multivariate risk model for GDM that included BMI.…”

“…H aptoglobin (Hp) is an acute-phase protein synthesized in the liver and, to some extent, in fat tissue (1) in response to interleukin 6 -type cytokines. The Hp gene is located on the long arm of chromosome 16 (16q22.3) (2).…”