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Environmental Toxicants and NAFLD: A Neglected yet Significant Relationship

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Abstract

The liver is an organ of vital importance in the body; it is the center of metabolic activities and acts as the primary line of defense against toxic compounds. Exposure to environmental toxicants is an unavoidable fallout from rapid industrialization across the world and is even higher in developing countries. Technological development and industrialization have led to the release of toxicants such as pollutant toxic gases, chemical discharge, industrial effluents, pesticides and solvents, into the environment. In the last few years, a growing body of evidence has shed light on the potential impact of environmental toxicants on liver health, in particular, on non-alcoholic fatty liver disease (NAFLD) incidence and progression. NAFLD is a multifactorial disease linked to metabolic derangement including diabetes and other complications. Environmental toxicants including xenobiotics and pollutants may have a direct or indirect steatogenic/fibrogenic impact on the liver and should be considered as risk factors associated with NAFLD. This review discusses the contribution of environmental toxicants toward the increasing disease burden of NAFLD.

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Abbreviations

NASH:

Non-alcoholic steatohepatitis

NAFLD:

Non-alcoholic fatty liver disease

HCC:

Hepatocellular carcinoma

ALT:

Alanine transaminase

POPs:

Persistent organic pollutants

PCB:

Poly chlorinated biphenyls

PAHs:

Poly aromatic hydrocarbons

DDT:

Dichlorodiphenyltrichloroethane

ROS:

Reactive oxygen species

BPA:

Bis phenol A

CVD:

Cardiovascular disease

TG:

Triglyceride

T2D:

Type 2 diabetes

HFD:

High fat diet

VOCs:

Volatile organic compounds

HSC:

Hepatic stellate cells

BAP:

Benzo alpha pyrene

PXR:

Pregnane X receptor

AhR:

Aryl hydrocarbon receptors

PPAR:

Peroxisome proliferator-activated receptor

SREBP:

Sterol regulatory element-binding proteins

TCDD:

2,3,7,8-Tetrachlorodibenzo-p-dioxin

CAR:

Constitutive androstane receptor

HNF4α:

Hepatocyte nuclear factor 4 alpha

PFAS:

Per- and polyfluoroalkyl substances

TAFLD:

Toxicant-associated fatty liver diseases

NF-κB:

Nuclear factor-κB

TLR4:

Toll-like receptor 4

IR:

Insulin resistance

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Acknowledgments

This work was supported by the ICMR (59/05/2019/ONLINE/BMS/TRM), SERB (SRG/2019/000398) awarded to Sinha RA.

Dr. Rohit A. Sinha, Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. Email: anthony.rohit@gmail.com; rasinha@sgpgi.ac.in

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    Sangam Rajak, Sana Raza, Archana Tewari & Rohit A. Sinha

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Rajak, S., Raza, S., Tewari, A. et al. Environmental Toxicants and NAFLD: A Neglected yet Significant Relationship. Dig Dis Sci 67, 3497–3507 (2022). https://doi.org/10.1007/s10620-021-07203-y

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