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. 2014 Dec 16:14:208.
doi: 10.1186/s12876-014-0208-8.

Expression of NALPs in adipose and the fibrotic progression of non-alcoholic fatty liver disease in obese subjects

Rohini Mehta  1   2 , Arpan Neupane  3   4 , Lei Wang  5   6 , Zachary Goodman  7   8 , Ancha Baranova  9   10 , Zobair M Younossi  11   12
Affiliations

Expression of NALPs in adipose and the fibrotic progression of non-alcoholic fatty liver disease in obese subjects

Rohini Mehta et al. BMC Gastroenterol. .

Abstract

Background: Visceral obesity is often accompanied by non-alcoholic fatty liver disease (NAFLD). Activation of NACHT, LRR and PYD domains-containing proteins (NALPs) may contribute to the release of pro-inflammatory cytokines by adipose and the obesity-associated progression of NAFLD to non-alcoholic steatohepatitis (NASH).

Methods: We analyzed visceral adipose expression of various NALPs and its downstream effectors caspase-1, ASC (Apoptosis-associated speck-like protein containing a CARD), IL-18 (Interleukin-18) and IL-1β (Interleukin- 1Beta) in obese subjects (BMI ≥ 35) with biopsy proven NAFLD.

Results: In adipose samples collected from NASH and pericellular fibrosis patients cohorts, expression levels of NALPs and IL-1β were lower than that in non-NASH patients. In portal fibrosis, the levels of mRNA encoding anti-inflammatory NALP6 were upregulated. The expression levels of all NALPs were significantly co-correlated. Circulating IL-18 levels were associated with increased liver injury markers AST and ALT and portal fibrosis.

Conclusion: Our observations point at a possible shift in inflammation and fibrotic response from adipose tissue to liver and a possible negative feedback regulation of tissue inflammation that may instigate NAFLD severity.

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Figures

Figure 1
Figure 1
Significantly altered gene expression in presence of pericellular fibrosis vs absence of pericellular fibrosis. A.) NALP4 gene expression; B.) IL1B gene expression.
Figure 2
Figure 2
Significantly altered gene expression in presence of NASH vs non-NASH NAFLD.
Figure 3
Figure 3
Significantly altered targets in presence of portal fibrosis vs absence of portal fibrosis. A.) NALP6 gene expression; B.) Circulating IL18 levels.
See this image and copyright information in PMC

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