FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys

Birgitte Andersen, Ellen M. Straarup, Kristy M. Heppner, Diana L. Takahashi, Virginia Raffaele, Gregory Dissen, Katherine Lewandowski, Thóra B. Bödvarsdottir, Kirsten Raun, Kevin Grove, Paul Kievit

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Methods: Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. Results: On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA1C. Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. Conclusion: In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Obesity
DOIs
StateAccepted/In press - Jun 11 2018

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Macaca mulatta
Bone Density
Eating
Fats
Body Weight
Hydrocortisone
Glucose
Insulin Resistance
Triglycerides
fibroblast growth factor 21
Bone and Bones
VLDL Cholesterol
Clinical Chemistry
High Fat Diet
Bone Resorption
Dyslipidemias
Body Composition
Lipid Metabolism
Animal Models
Obesity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys. / Andersen, Birgitte; Straarup, Ellen M.; Heppner, Kristy M.; Takahashi, Diana L.; Raffaele, Virginia; Dissen, Gregory; Lewandowski, Katherine; Bödvarsdottir, Thóra B.; Raun, Kirsten; Grove, Kevin; Kievit, Paul.

In: International Journal of Obesity, 11.06.2018, p. 1-10.

Research output: Contribution to journalArticle

Andersen, B, Straarup, EM, Heppner, KM, Takahashi, DL, Raffaele, V, Dissen, G, Lewandowski, K, Bödvarsdottir, TB, Raun, K, Grove, K & Kievit, P 2018, 'FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys', International Journal of Obesity, pp. 1-10. https://doi.org/10.1038/s41366-018-0080-7
Andersen, Birgitte ; Straarup, Ellen M. ; Heppner, Kristy M. ; Takahashi, Diana L. ; Raffaele, Virginia ; Dissen, Gregory ; Lewandowski, Katherine ; Bödvarsdottir, Thóra B. ; Raun, Kirsten ; Grove, Kevin ; Kievit, Paul. / FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys. In: International Journal of Obesity. 2018 ; pp. 1-10.
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abstract = "Objective: Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Methods: Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. Results: On average, FGF21 decreased body weight by 17.6 ± 1.6{\%} after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA1C. Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. Conclusion: In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.",
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AU - Straarup, Ellen M.

AU - Heppner, Kristy M.

AU - Takahashi, Diana L.

AU - Raffaele, Virginia

AU - Dissen, Gregory

AU - Lewandowski, Katherine

AU - Bödvarsdottir, Thóra B.

AU - Raun, Kirsten

AU - Grove, Kevin

AU - Kievit, Paul

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N2 - Objective: Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Methods: Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. Results: On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA1C. Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. Conclusion: In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

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