HT-VA restores cholesterol to control-diet levels and maintains lower triglycerides compared with semaglutide in western diet-fed female mice
Treatment preserved hepatic autophagy and maintained normal liver cellular homeostasis
Findings support continued development of HT-VA for metabolic dysfunction associated with obesity and MASLD
NEW YORK, March 10, 2026 /PRNewswire/ -- Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company focused on developing innovative therapies for patients with unmet medical needs, today announced new female-specific preclinical results from the second phase of its metabolic disease study evaluating glial cell-derived neurotrophic factor (GDNF).
The second phase of the study evaluated serum liver biochemistry and hepatic molecular pathways in female mice fed a western diet to model metabolic dysfunction associated with obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
Results demonstrate that GDNF improved lipid metabolism biomarkers and preserved key cellular pathways in the liver compared with western diet controls and the GLP-1 agonist Semaglutide.
GDNF Restores Elevated Cholesterol Levels to Control-Diet Range in Western Diet-Fed Female Mice
Female mice fed a western diet demonstrated increased serum cholesterol levels relative to control diet animals.
Treatment with GDNF restored cholesterol concentrations to levels comparable with control diet-fed mice, indicating improved lipid metabolism in the diet-induced metabolic dysfunction model.
GDNF Maintains Lower Triglyceride Levels While Semaglutide Increases Triglycerides in Female Mice
Female mice treated with Semaglutide while on a western diet showed increased serum triglyceride levels.
In contrast, GDNF-treated western diet mice maintained lower triglyceride levels, demonstrating a more favorable lipid profile in this study.
Albumin and Alkaline Phosphatase Remain Stable Across Female Treatment Groups
Analysis of liver biochemistry markers demonstrated:
- No change in albumin (ALB) levels across diets or treatments
- No significant change in alkaline phosphatase (ALP)
These findings indicate liver synthetic function remained stable across female treatment groups.
GDNF Preserves Hepatic Autophagy While Semaglutide Increases p62 Accumulation
Evaluation of liver autophagy markers revealed:
- Semaglutide increased p62/SQSTM1 levels in western diet-fed female mice
- GDNF treatment did not increase p62 expression
Accumulation of p62 is associated with impaired autophagic degradation, suggesting GDNF preserved normal cellular recycling pathways in the liver.
No Activation of Lipid Uptake or Lipogenesis Pathways Observed in Female Mice Treated with GDNF
Protein expression analysis showed:
- No change in PPAR? expression
- No change in CD36 expression
These proteins are associated with hepatic lipid uptake and fat accumulation, indicating that GDNF improved metabolic biomarkers without activating lipogenic pathways.
Semaglutide Increases Hepatic AKT Signaling While GDNF Shows No Change
Western diet-fed female mice treated with Semaglutide demonstrated increased phosphorylation of AKT (pAKT) in liver tissue.
By contrast, GDNF treatment did not significantly alter pAKT signaling, highlighting a distinct molecular signaling profile.
Study Overview
The second phase of the preclinical study focused on evaluating liver metabolism and molecular signaling pathways in female mice.
Study design included:
- Female mice fed control diet or western diet for eight weeks
- Four weeks of treatment with GDNF, semaglutide, or vehicle
- Evaluation of serum liver biochemistry and hepatic protein expression related to lipid metabolism, autophagy, and apoptosis
Each treatment group included 8-10 animals, with results reported as mean ± SEM.
About Hoth Therapeutics, Inc.
Hoth Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative, impactful, and ground-breaking treatments with a goal to improve patient quality of life. We are a catalyst in early-stage pharmaceutical research and development, elevating drugs from the bench to pre-clinical and clinical testing. Utilizing a patient-centric approach, we collaborate and partner with a team of scientists, clinicians, and key opinion leaders to seek out and investigate therapeutics that hold immense potential to create breakthroughs and diversify treatment options. To learn more, please visit https://ir.hoththerapeutics.com/.
Forward-Looking Statement
This press release includes forward-looking statements based upon Hoth's current expectations, which may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, and are subject to substantial risks, uncertainties, and assumptions. These statements concern Hoth's business strategies; the timing of regulatory submissions; the ability to obtain and maintain regulatory approval of existing product candidates and any other product candidates we may develop, and the labeling under any approval we may obtain; the timing and costs of clinical trials, and the timing and costs of other expenses; market acceptance of our products; the ultimate impact of the current coronavirus pandemic, or any other health epidemic, on our business, our clinical trials, our research programs, healthcare systems, or the global economy as a whole; our intellectual property; our reliance on third-party organizations; our competitive position; our industry environment; our anticipated financial and operating results, including anticipated sources of revenues; our assumptions regarding the size of the available market, benefits of our products, product pricing, and timing of product launches; management's expectation with respect to future acquisitions; statements regarding our goals, intentions, plans, and expectations, including the introduction of new products and markets; and our cash needs and financing plans. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. You should not place reliance on these forward-looking statements, which include words such as "could," "believe," "anticipate," "intend," "estimate," "expect," "may," "continue," "predict," "potential," "project" or similar terms, variations of such terms, or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section titled "Risk Factors" in Hoth's most recent Annual Report on Form 10-K and Hoth's other filings made with the U. S. Securities and Exchange Commission. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates, and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance, or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events, or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.
Investor Contact:
LR Advisors LLC
Email: [email protected]
www.hoththerapeutics.com
Phone: (678) 570-6791
SOURCE Hoth Therapeutics, Inc.
