Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents
Open accessAbstract
Aim: To investigate the role of glucose‐dependent insulinotropic polypeptide receptor (GIPR) agonists alone or combined with glucagon‐like peptide‐1 receptor (GLP‐1R) agonists to regulate palatable food intake and the role of specific macronutrients in these preferences. Methods: To understand this regulation, we treated mice and rats on several choice diet paradigms of chow and a palatable food option with individual or dual GIPR and GLP‐1R agonists. Results: In mice, the dual agonist tirzepatide suppressed total caloric intake, while promoting the intake of chow over a high fat/sucrose diet. Surprisingly, GIPR agonism alone did not alter food choice. The food intake shift observed with tirzepatide in wild‐type mice was completely absent in GLP‐1R knockout mice, suggesting that GIPR signalling does not regulate food preference. Tirzepatide also selectively suppressed the intake of palatable food but not chow in a rat two‐diet choice model. This suppression was specific to lipids, as GLP‐1R agonist and dual agonist treatment in rats on a choice paradigm assessing individual palatable macronutrients robustly inhibited the intake of Crisco (lipid) without decreasing the intake of a sucrose (carbohydrate) solution. Conclusions: Decreasing preference for high‐caloric, high‐fat foods is a powerful action of GLP‐1R and dual GIPR/GLP‐1R agonist therapeutics, which may contribute to the weight loss success of these drugs.
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Bariatric surgery still stands as the benchmark for weight loss, triggering weight reduction of approximately 25-30% within a 1-2 year period.
“In conclusion, bariatric surgery still stands as the benchmark for weight loss, triggering weight reduction of ~25-30% within a 1-2 year period175.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [175]
The Results describe tirzepatide-related weight loss in mice and rats over days or weeks, not outcomes after bariatric surgery. Searches for bariatric surgery, a 25–30% reduction, and a 1–2-year period found no passage in our copy addressing the claim. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe ability of these medications to selectively reduce the intake of high-fat, high-sugar palatable foods makes them strategic in nutritional re-education.
“The ability of these medications to selectively reduce the intake of high-fat, high-sugar palatable foods [60,61,75] makes them strategic in nutritional re-education.”
From Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review (2025) · cites this paper as [75]
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- Authors
- Geisler, C. E., Antonellis, M. P., Trumbauer, W., Martin, J. A., Coskun, T., Samms, R. J., & Hayes, M. R.
- Affiliations
- University of Pennsylvania (US)
- Eli Lilly (United States) (US)
- Diabetes, Obesity and Complications, Lilly Research Laboratories Eli Lilly and Company Indianapolis Indiana
- Corresponding author
- Hayes, Matthew R.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2022-09-12
- Volume
- 25
- Issue
- 1
- Pages
- 56-67
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC10362946
- OpenAlex
- W4292509485
- Cited by
- 51
- References
- 42
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 11 · 2023: 6
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- National Institute of Diabetes and Digestive and Kidney Diseases (DK021397)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- tirzepatide, glucose-dependent insulinotropic polypeptide receptor, GLP-1 receptor, GIP/GLP-1 receptor agonist, palatable food intake, food preferences, fat preference, high-fat sucrose diet, macronutrient intake, energy intake, weight loss
- MeSH terms
- Animals, Eating, Rodentia, Weight Loss, Mice, Rats
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