PPID, Pergolide and muscle atrophy

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      This is a well-designed experiment with surprising results, at least to me. The finding that pergolide did not improve the muscle mass runs counter to my experience with pergolide. They did find decrease in the odd adipose appearance of PPID horses and did find a positive effect on insulin regulation, the chief predictor of future laminitis episodes. Perhaps the reason for this is at the time that pergolide is instituted we also begin a high energy, high protein, lowered carb diet and that is the reason for the overall increase in condition. See the article for more on this.
      DrO

      Markers of muscle atrophy and impact of treatment with pergolide in horses with pituitary pars intermedia dysfunction and muscle atrophy
      Domest Anim Endocrinol. 2021 Feb 18;76:106620. doi: 10.1016/j.domaniend.2021.106620. Online ahead of print.
      Authors
      H E Banse 1 , A E Whitehead 2 , D McFarlane 3 , P K Chelikani 4
      Affiliations

      1 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: hbanse1@lsu.edu.
      2 Department of Veterinary and Clinical Diagnostic Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada.
      3 Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA.
      4 School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA.

      PMID: 33740552
      DOI: 10.1016/j.domaniend.2021.106620

      Abstract

      Pituitary pars intermedia dysfunction (PPID) is a common endocrine disorder of aged horses, with muscle atrophy as one of the clinical signs. We sought to compare muscle mass and regulation of skeletal muscle proteolysis between horses with PPID and muscle atrophy to older horses without PPID, and to assess the impact of treatment with pergolide (dopaminergic agonist) on PPID horses. We hypothesized that PPID-associated muscle atrophy is a result of increased proteolysis, and that markers of muscle atrophy and proteolysis would improve over time with pergolide treatment. Markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis (muscle atrophy F- box/atrogin 1 [MAFbx1], muscle RING finger 1 [MuRF1], Bcl2/adenovirus EIV 19kD interacting protein 3 [Bnip3], and microtubule-associated light chain 3 [LC3]) were compared between PPID and control horses. PPID horses were treated for 12 weeks with either pergolide or placebo. Dose of pergolide was adjusted based upon monthly measurement of adrenocorticotropin, and markers of muscle atrophy, adiposity, insulin regulation, skeletal muscle composition, and proteolysis were compared after 12 weeks of treatment. Horses with PPID exhibited increased transcript abundance of MuRF1 (P= 0.04) compared to control. However, no difference was observed in transcript abundance of markers of proteolysis with treatment (P ≥ 0.25). Pergolide treated horses lost weight (P = 0.02) and improved fasting insulin (P = 0.02), while placebo treated horses gained weight and rump fat thickness (P = 0.02). Findings from this study suggest that treatment with pergolide may promote weight loss and improve insulin regulation in horses with PPID, but does not impact muscle mass or markers of muscle proteolysis.

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