Absalon Gutierrez
University of Texas Health Science Center at Houston, TX·Medicine & Clinical Research
Hormone-based drugs that mimic GLP-1 (glucagon-like peptide-1, a gut hormone released after eating that boosts insulin and curbs appetite) have transformed treatment for obesity and diabetes. Two problems remain, and both come down to the fact that people respond differently.
- Fields
Medicine & Clinical Research
Genetics
Pharmacology
- Topics
GLP-1 receptor agonist
obesity
prediabetes
- Grants
- 2 known grants, through May 2031
What they work on
- Identify molecular signatures of weight and energy-expenditure change after GLP-1 receptor agonist withdrawal using RNA sequencing and DNA methylation analysis of abdominal subcutaneous fat biopsies in 100 adults with obesity.
- Find parallel transcriptomic and methylation signatures in peripheral blood that track weight and energy-expenditure changes after drug discontinuation, as a more accessible readout than fat biopsy.
- Probe sources of metabolic variability during GLP-1 drug administration and withdrawal using mixed meal tolerance tests with metabolite profiling and measures of insulin action, plus indirect calorimetry and DXA body composition scans.
- Test whether gene-expression-regulating variants (eQTLs) of 11 candidate genes in metabolic tissues predict physiological response to endogenous and drug-delivered GLP-1 in 300 Mexican-American adults with prediabetes.
- Use RNA sequencing of blood before and after GLP-1 therapy to discover new eQTLs that predict treatment response and to build risk-based prediction models for Hispanic/Latino patients.
- Determine the broader health consequences of candidate genes and newly found eQTLs by phenome-wide analysis in BioVU, a large biobank linking genotypes to electronic health records.
More about the research
First, when patients stop these drugs, most regain weight and their metabolic risk returns, but the degree varies widely. Second, among people with prediabetes, some get far more benefit from GLP-1 than others, and genetic studies so far have not explained why. Both projects run human clinical studies and combine physiology with genomics to link an individual's genes and gene activity to how their body actually responds to this hormone, with the goal of more individualized treatment.
Why it matters
Together these studies could make obesity and diabetes treatment more personalized. Identifying the molecular pathways behind weight regain after GLP-1 drugs are stopped could reveal targets for add-on therapies that keep weight and metabolic risk down. Linking gene-expression variants to measured GLP-1 response in Mexican-American adults with prediabetes may help predict who benefits from these drugs in a population underrepresented in pharmacogenomic research, informing diabetes prevention, weight loss and cardiovascular and kidney risk reduction.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Andrea Hevener
University of California-San Diego, CA·Physiology
Provide measurements of hormone sensitivity, body composition and energy balance in genetically engineered mice, including indirect calorimetry and glucose and insulin tolerance tests.
Dongmin Liu
Virginia Polytechnic Institute and State University, VA·Pharmacology
Characterize the anti-diabetic and anti-obesity effects of daily oral elenolic acid in diet-induced obese and db/db diabetic mice, using metabolic profiling and euglycemic-hyperinsulinemic clamps to measure insulin sensitivity.
Jonathan Campbell
Duke University, NC·Physiology
Test whether pericytes, cells lining blood vessels, are the main GIP receptor (GIPR)-expressing cells in fat tissue, using mouse models that mark and lineage-trace GIPR-positive cells over time.
The school
University of Texas Health Science Center at Houston: 25 labs on PI Pages, $419M a year on research, 340 research doctorates a year.
More about University of Texas Health Science Center at Houston
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