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Cited by 96Thyroid Disorders and TreatmentsRegulation of Appetite and ObesityAdipose Tissue and Metabolism

Anti-obesity, anti-diabetic, and lipid lowering effects of the thyroid receptor β subtype selective agonist KB-141

Bryzgalova, Galina, Effendic, Suad, Khan, Akhtar, Rehnmark, Stefan, Barbounis, Peter, Boulet, Jamie, Dong, Gao, Singh, Rajni +5 more·2008·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2008.06.010
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Abstract

Selective thyroid hormone receptor subtype-beta (TRbeta) agonists have received attention as potential treatments for hypercholesterolemia and obesity, but have received less attention as treatments for diabetes, partly because this condition is not improved in thyroid hormone excess states. The TRbeta selective agonist KB-141 induces 5-10% increases in metabolic rate and lowering of plasma cholesterol levels without tachycardia in lean rats, unlike the major active thyroid hormone, T3. In the current study, we determined whether KB-141 promotes weight loss in obese animals and whether it exhibits anti-diabetogenic effects. Body weight, adiposity (DEXA), and lipid levels were examined following p.o. administration of KB-141 to obese Zucker fa/fa rats at 0.00547-0.547 mg/kg/day for 21 days, and in ob/ob mice at 0.5mg/kg/day KB-141 for 7 days. In rats, KB-141 reduced body weight by 6 and 8%, respectively, at 0.167 and 0.0547 mg/kg/day without tachycardia and adiposity was reduced at 0.167 mg/kg/day (5-6%). In ob/ob mice, KB-141 lowered serum cholesterol (35%), triacylglycerols (35%) and both serum and hepatic free fatty acids (18-20%) without tachycardia. Treatment of ob/ob mice with KB-141 (0.0547 or 0.328 mg/kg/day over 2 weeks) improved glucose tolerance and insulin sensitivity in a dose-dependent manner with no effect on heart rate. Thus, KB-141 elicits anti-obesity, lipid lowering and anti-diabetic effects without tachycardia suggesting that selective TRbeta activation may be useful strategy to attenuate features of the metabolic syndrome.

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Crossref · 10.1016/j.jsbmb.2008.06.010

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  • Two selective TH mimetics, GC-1 and KB141, can promote fat loss in rodents without causing unwanted effects on heart or muscle.

    “Indeed, two of the selective TH mimetics, GC-1 and KB141, can promote fat loss in rodents without causing unwanted effects on heart or muscle 145,146.”

    From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [146]

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Authors
Bryzgalova, G., Effendic, S., Khan, A., Rehnmark, S., Barbounis, P., Boulet, J., Dong, G., Singh, R., Shapses, S., Malm, J., Webb, P., Baxter, J. D., & Grover, G. J.
Affiliations
  • Karolinska Institutet (SE)
  • Karo Pharma (Sweden) (SE)
  • Eurofins (United States) (US)
  • Rutgers, The State University of New Jersey (US)
  • University of California, San Francisco (US)
Corresponding author
Grover, Gary J.
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2008-09
Volume
111
Issue
3-5
Pages
262-267
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2008.06.010
OpenAlex
W2015246839
Cited by
94
References
30
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 11 · 2013: 9 · 2012: 8
FWCI
6.51
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
thyroid hormone receptor beta, obesity, diabetes mellitus, hypercholesterolemia, lipid lowering, weight loss, adiposity, glucose tolerance, insulin sensitivity, metabolic syndrome, ob/ob mice, Zucker fatty rats, free fatty acids, triglycerides, tachycardia
MeSH terms
Animals, Hypolipidemic Agents, Body Weight, Diabetes Mellitus, Female, Humans, Hypercholesterolemia, Hypoglycemic Agents, Mice, Obese, Obesity, Phenyl Ethers, Phenylacetates, Rats, Zucker, Molecular Structure, Anti-Obesity Agents, Thyroid Hormone Receptors beta, Mice, Rats

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