Related Experiment Video
Updated: May 9, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Are glyphosate or glyphosate-based herbicides linked to metabolic dysfunction-associated steatotic liver disease
Luana Riechelmann-Casarin1, Leticia Cardoso Valente1, Rosemari Otton2
1São Paulo State University (UNESP), Experimental Research Unit (UNIPEX), Botucatu Medical School, Brazil.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30 % of the world's population, increasing its prevalence by 50 % in the last three decades. MASLD pathogenesis is considered multiaxial, involving disturbances in the liver, adipose tissue (AT), and gut microbiome. In parallel with MASLD increasing trends, the total herbicide use has nearly tripled over the last three decades. Glyphosate (GLY) is the most used herbicide worldwide (825 mi kg/year). The intensive use of GLY-based herbicides (GBH) - largely driven by the adoption of glyphosate-tolerant genetically modified crops over the past two decades - has led to environmental (soil and water) and food contamination, resulting in continuous human exposure. Emerging (pre)clinical data highlights the significant implications of this herbicide on MASLD, marking a critical research area. Thus, this narrative review paper aimed at gathering and evaluating all epidemiological and (pre)clinical data on the implications of GLY or GBH on MASLD outcomes. Our work encompassed literature published between 2008-2025. Human urinary GLY levels are associated with different MASLD outcomes (steatosis risk, advanced fibrosis, increased transaminases) and comorbidities (higher risk for metabolic syndrome, diabetes, obesity and cardiovascular diseases) (6 studies). In vitro data indicate that GBH/GLY cause oxidative stress, genomic instability, apoptosis, and membrane disruption in hepatocytes, while promoting apoptosis and lipid peroxidation in (pre)adipocytes and cytokine production in monocytes (15 studies). In rodent studies (21 studies), GLY/GBH - in doses based on human exposure/toxicological limits - induces inflammatory and oxidative responses in the liver and AT, while causing dysbiosis and metabolic alterations in the gut microbiome axis. In the light of populational-, cell- and animal-based evidence, GLY/GBH disturbs key axis of MASLD pathogenesis and is hypothesized to be associated with its clinical outcomes.
Insights
Glyphosate-based herbicides (GBH) are linked to metabolic dysfunction-associated steatotic liver disease (MASLD). This review connects human exposure to GBH with MASLD development and progression, supported by cellular and animal studies.
Area of Science:
- Environmental Health
- Hepatology
- Toxicology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 30% of the global population, with a 50% increase in prevalence over three decades.
- Global herbicide use, particularly glyphosate (GLY) and glyphosate-based herbicides (GBH), has tripled in the last 30 years, leading to widespread environmental and food contamination.
- Emerging evidence suggests a significant link between GLY/GBH exposure and MASLD pathogenesis and outcomes.
Purpose of the Study:
- To conduct a narrative review of epidemiological and preclinical data on the implications of GLY or GBH on MASLD.
- To evaluate the association between human GLY exposure and MASLD outcomes and comorbidities.
- To synthesize findings from in vitro and animal studies regarding GLY/GBH effects on liver, adipose tissue, and gut microbiome.
Main Methods:
- Literature search encompassing epidemiological, in vitro, and animal studies published between 2008-2025.
- Analysis of human urinary GLY levels in relation to MASLD outcomes and metabolic comorbidities.
- Review of experimental data on cellular mechanisms and in vivo effects of GLY/GBH in rodent models.
Main Results:
- Human studies show associations between urinary GLY levels and MASLD risk, advanced fibrosis, elevated transaminases, and comorbidities like metabolic syndrome, diabetes, and obesity.
- In vitro studies demonstrate that GBH/GLY induce oxidative stress, genomic instability, apoptosis, and membrane disruption in liver cells, and promote apoptosis and lipid peroxidation in adipocytes.
- Rodent studies, using doses relevant to human exposure, reveal that GLY/GBH induce inflammatory and oxidative responses in the liver and adipose tissue, and cause gut dysbiosis and metabolic alterations.
Conclusions:
- Glyphosate and glyphosate-based herbicides disrupt key pathways involved in MASLD pathogenesis, including liver, adipose tissue, and gut microbiome.
- Population, cellular, and animal-based evidence strongly suggests a link between GLY/GBH exposure and adverse MASLD clinical outcomes.
- Further research is critical to fully elucidate the role of GLY/GBH in the increasing global burden of MASLD.
Related Concept Videos
01:24Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
01:24Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
01:30Liver Physiology
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
01:26Diseases of the Liver and Gallbladder
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
01:19Overview of Carbohydrate Metabolism
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
01:40Overview of Metabolism
Plant Metabolism
Sunlight, the primary source of energy in plants, is first absorbed by the chlorophyll pigments present in their leaves. Plants then use this energy to carry out photosynthesis, where water is oxidized into oxygen and carbon dioxide...