title: Weight Loss Partially Restores Glucose-Driven Betatrophin Response in Humans.
abstract: BACKGROUND
  Recently a potential role of betatrophin was shown in the postprandial switch from lipid to glucose metabolism.
  
  
  OBJECTIVE
  The objective of the study was to analyze whether obesity is associated with altered postprandial betatrophin response and whether this could be restored by weight loss. Design, Setting, Participants, and Intervention: Oral glucose load was performed in 12 lean individuals at baseline as well as in 20 obese subjects before and after a 12-week structured weight-loss program at an endocrinology research center. Euglycemic hyperinsulinemic clamps were performed in the obese cohort. The effect of insulin and different glucose concentrations on betatrophin expression were analyzed in 3T3-L1 adipocytes.
  
  
  METHODS
  Circulating betatrophin levels during a glucose challenge were measured.
  
  
  RESULTS
  The betatrophin level decreases after an oral glucose intake (P < .001). This correlates with the increase of glucose levels (r = -0.396; P < .05). Hyperinsulinemia results in an increase of betatrophin. In vitro experiments in 3T3-L1 adipocytes confirmed that insulin and low glucose concentration increases betatrophin expression, whereas a further elevation of glucose levels blunts this effect. Obese subjects are characterized by lower fasting betatrophin (600.6 ± 364.4 vs 759.5 ± 197.9 pg/mL; P < .05) and a more pronounced betatrophin suppression during the glucose challenge. The impaired betatrophin response in obese subjects is restored after weight loss and is comparable with lean individuals.
  
  
  CONCLUSIONS
  Obesity is associated with increased betatrophin suppression after an oral glucose load, which is driven by increased hyperglycemia. Given the metabolic properties of betatrophin, this may indicate that betatrophin is tightly linked to obesity-associated metabolic disturbances. In line with such an assumption, weight loss almost completely eliminated this phenomenon.
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Maurer
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brachs
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Decker
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Brachs
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Leupelt
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Jumpertz von Schwartzenberg
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ernert
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bobbert
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.affiliation: Medical Clinic of Endocrinology, Diabetes, and Nutrition (L.M., S.B.,A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.) and Department of Pediatric Endocrinology and Diabetology (A.E., H.K.), Charité-Universitaetsmedizin Berlin, 10117 Berlin, Germany, Charité-Center for Cardiovascular Research (L.M., S.B., A.-M.D., M.B., V.L., R.J.v.S., T.B., J.S., K.M.), 10117 Berlin, Germany, and Clinical Research Unit (A.-M.D., K.M.), Berlin Institute of Health 10117 Berlin, Germany; and Experimental and Clinical Research Center (S.B., M.B., R.J.v.S., J.S., K.M.), 13125 Berlin, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Mai
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000378:metabolism*; D050154:Adiposity; D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D015331:Cohort Studies; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000628:therapy; D050177:Overweight / Q000097:blood* / Q000378:metabolism / Q000628:therapy; D036361:Peptide Hormones / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D019518:Postprandial Period; D015431:Weight Loss; D061217:Weight Reduction Programs
chemical_list: C576683:ANGPTL8 protein, human; C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D001786:Blood Glucose; D007328:Insulin; D036361:Peptide Hormones