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The aim of this study was to assess the effect of FGF21 on food intake, body weight, body composition, glucose homeostasis, bone mineral density (BMD), cortisol and growth hormone (GH) in obese minipigs. The pig is a unique model for studying FGF21 pharmacology as it does not express UCP1, unlike mice and humans. Twelve obese Göttingen minipigs with a mean body weight of 91.6 ± 6.7 kg (mean ± SD) received subcutaneously either vehicle (n = 6) or recombinant human FGF21 (n = 6) once daily for 14 weeks (0.1 mg/kg for 9.5 weeks and 0.3 mg/kg for 4.5 weeks). Treatment of obese minipigs with FGF21 led to a 50% reduction in food intake and a body weight loss of, on average, 18 kg compared to the vehicle group after 14 weeks of dosing. Glucose tolerance and insulin sensitivity, evaluated by intravenous glucose tolerance test, were significantly improved in the FGF21 group compared to the vehicle group at the end of the study. The plasma cortisol profile was unaffected by FGF21, whereas a small decrease in peak GH values was observed in the FGF21-treated animals after 7 to 9.5 weeks of treatment compared to the vehicle group. Whole-body BMD was not affected by 13 weeks of FGF21 dosing. Despite a lack of UCP-1 in obese minipigs, FGF21 treatment induced a significant weight loss, primarily a result of reduction in food intake, with no adverse effect on BMD or plasma cortisol.
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
February 2020,
International journal of obesity (2005),
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
June 2018,
International journal of obesity (2005),
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
October 2004,
Obesity research,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
August 2016,
Journal of pharmacokinetics and pharmacodynamics,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
January 1987,
Physiology & behavior,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
July 1982,
The Journal of clinical endocrinology and metabolism,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
November 2005,
The Journal of clinical investigation,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
July 1999,
Physiology & behavior,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
January 1982,
Peptides,
Berit Christoffersen, and
Ellen M Straarup, and
Kirsten Lykkegaard, and
Johannes J Fels, and
Kristian Sass-Ørum, and
Xujia Zhang, and
Kirsten Raun, and
Birgitte Andersen
January 2013,
American journal of translational research,
