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Updated: Aug 3, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
MPEP Attenuates Intrahepatic Fat Accumulation in Obese Mice
Andrea Ferrigno1,2, Marta Cagna1, Oriana Bosco1
1Unit of Cellular and Molecular Pharmacology and Toxicology, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
Abstract:
The blockade of metabotropic glutamate receptor type 5 (mGluR5) was previously found to reduce fat accumulation in HEPG2 cells. Here, we evaluated the effects of mGluR5 blockade in a mouse model of steatosis. Male ob/ob mice fed a high-fat diet were treated with MPEP or vehicle. After 7 weeks, liver biopsies were collected, and nuclei were isolated from fresh tissue. Lipid droplet area and collagen deposition were evaluated on tissue slices; total lipids, lipid peroxidation, and ROS were evaluated on tissue homogenates; PPARα, SREBP-1, mTOR, and NF-κB were assayed on isolated nuclei by Western Blot. Target genes of the above-mentioned factors were assayed by RT-PCR. Reduced steatosis and hepatocyte ballooning were observed in the MPEP group with respect to the vehicle group. Concomitantly, increased nuclear PPARα and reduced nuclear SREBP-1 levels were observed in the MPEP group. Similar trends were obtained in target genes of PPARα and SREBP-1, Acox1 and Acc1, respectively. MPEP administration also reduced oxidative stress and NF-κB activation, probably via NF-κB inhibition. Levels of common markers of inflammation (Il-6, Il1β and Tnf-α) and oxidative stress (Nrf2) were significantly reduced. mTOR, as well as collagen deposition, were unchanged. Concluding, MPEP, a selective mGluR5 negative allosteric modulator, reduces both fat accumulation and oxidative stress in a 7-week murine model of steatosis. Although underlying mechanisms need to be further investigated, this is the first in vivo study showing the beneficial effects of MPEP in a murine model of steatosis.
Insights
Blocking metabotropic glutamate receptor type 5 (mGluR5) with MPEP reduced fat accumulation and oxidative stress in a mouse model of steatosis. This study provides the first in vivo evidence of MPEP
Area of Science:
- Hepatology
- Metabolic Disorders
- Neuropharmacology
Background:
- Metabotropic glutamate receptor type 5 (mGluR5) blockade showed potential in reducing fat accumulation in cell models.
- Steatosis, characterized by fat buildup in the liver, is a growing health concern with limited treatment options.
Purpose of the Study:
- To investigate the in vivo efficacy of mGluR5 blockade using MPEP in a high-fat diet-induced mouse model of steatosis.
- To elucidate the molecular mechanisms underlying MPEP's effects on liver fat accumulation, oxidative stress, and inflammation.
Main Methods:
- Male ob/ob mice on a high-fat diet were treated with MPEP or vehicle for 7 weeks.
- Liver tissues were analyzed for lipid content, collagen deposition, oxidative stress markers (ROS, lipid peroxidation), and key protein/gene expression (PPARα, SREBP-1, mTOR, NF-κB, Acox1, Acc1, Il-6, Il1β, Tnf-α, Nrf2).
Main Results:
- MPEP treatment significantly reduced hepatic steatosis and hepatocyte ballooning compared to vehicle.
- MPEP administration led to increased nuclear PPARα and decreased nuclear SREBP-1 levels, alongside changes in their target genes.
- Oxidative stress, NF-κB activation, and inflammatory markers were significantly reduced in the MPEP group.
Conclusions:
- MPEP, a selective mGluR5 negative allosteric modulator, effectively reduces fat accumulation and oxidative stress in a murine model of steatosis.
- The findings suggest a therapeutic potential for mGluR5 blockade in managing non-alcoholic fatty liver disease (NAFLD).
- Further research is warranted to fully understand the underlying mechanisms and long-term effects of MPEP in steatosis.
