Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly obese patients: a cohort study

Abstract

BackgroundIn animal experiments persistent organic pollutants (POPs) cause hepatosteatosis. In epidemiological studies POPs have positive associations with serum markers of nonalcoholic fatty liver disease (NAFLD) and together with obesity synergistic association with insulin resistance. Because insulin resistance and obesity are critical in NAFLD pathogenesis, we investigated the association of serum pollutant levels with liver histology and alanine aminotransferase (ALT) in morbidly obese.MethodsLiver biopsies were from 161 participants of the Kuopio Obesity Surgery Study (KOBS) who underwent bariatric surgery 2005–2011. Liver histology was categorized as normal, steatosis and non-alcoholic steatohepatitis (NASH). Liver phenotype at baseline and ALT at baseline and 12 months post-surgery were correlated to serum POP concentrations at respective time points. As lipophilic POPs concentrate to smaller fat volume during weight loss, serum levels before and 12 months after bariatric surgery were compared.ResultsBaseline serum concentration of PCB-118, β-HCH and several PFAAs had an inverse association with lobular inflammation possibly due to changes in bile acid metabolism. ALT had negative associations with many POPs at baseline that turned positive at 12 months after major clinical improvements. There was an interaction between some POPs and sex at 12 months, and in stratified data positive associations were observed mainly in females but not in males.ConclusionsWe found a negative association between serum concentrations of PCB-118, β-HCH and several PFAAs with lobular inflammation at baseline. Positive POPs-ATL associations at 12 months among women suggest that increased POP concentrations may decrease the degree of liver recovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0066-z) contains supplementary material, which is available to authorized users.

Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism

“…Recently, there has been more focus on the influences of OCPs on metabolism192021. However, the underlying molecular mechanisms for how OCPs would lead to disorders in fatty acid metabolism have not yet been fully clarified.…”

PCB-associated steatohepatitis and the role of nuclear receptors.

“…ƩPCBs has been previously associated with liver disease in other epidemiologic studies 37,[95][96][97][98][99] .…”

“…As mentioned previously, the effects of dioxin-like chemicals have historically been attributed to AhR-mediated mechanisms, and the TEQ, by estimating the cumulative, weighted load of AhR ligands, can be used as an exposure variable to explore the Note that all congeners given in this table had at least a 96.7% detection rate. No significant differences were seen for PCB congeners 74,87,99,118,138,146,153,156,157,167,170,177,180,183,189,194,196,199,206,209. Table 25.…”

“…All (ƩPCB) 28, 44, 49, 52, 66, 74, 87, 99, 101, 105, 110, 118, 128, 138-158, 146, 149, 151, 153, 156, 157, 167, 170, 172, 177, 178, 180, 183, 187, 189, 194, 195, 196-203, 199, 206, 209 Ortho-Substituted (ƩPCB-O) 28,44,49,52,66,74,87,99,101,105,110,118,128,138,146,149,151,153,156,157,167,170,172,177,178,180,183,187,189,194,195,196,199,206,209 Tri-and Tetra-ortho (ƩPCB-TO) 149, 151, 177, 178, 183, 187, 195, 196-203, 199, 206, 209 Di-Ortho (ƩPCB-DO) 44 183,187,194,195,196,199,206,209 Estrogen receptor (estrogen...…”

“…Previous epidemiologic studies have demonstrated dose responses for PCBs in liver disease [95][96][97][98][99] , and animal studies have demonstrated interactions between PCBs and diet-induced obesity in steatohepatitis 22,23 . Univariate analysis was performed in the ACHS-1 cohort to determine associations between ƩPCBs and the liver injury biomarkers used to derive the liver injury categories (Table 13).…”