Rocco Barazzoni1, Gianluca Gortan Cappellari2, Michela Zanetti2, Katherine A Klaus3, Annamaria Semolic2, Matthew L Johnson3, K Sreekumaran Nair4. 1. Dept. of Medical, Surgical and Health Sciences - University of Trieste, Italy and Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy. Electronic address: barazzon@units.it. 2. Dept. of Medical, Surgical and Health Sciences - University of Trieste, Italy and Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy. 3. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA. 4. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA. Electronic address: nair@mayo.edu.
Abstract
BACKGROUND & AIMS: Unacylated ghrelin (UnAG) modulates insulin sensitivity. Low plasma UnAG occurs in obesity and potentially contributes to obesity-associated insulin resistance. We hypothesized that improvements in insulin sensitivity in obese people induced by moderate caloric restriction (CR) may be paralleled and at least in part explained by concurrent increases in UnAG levels. METHODS: 20 general community obese people were randomly assigned to 16-week CR (n = 11) or control diet (n = 9). We investigated the impact of CR on the interaction between insulin sensitivity changes [area under the curve (AUCg) of glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamp] and plasma total (TotalG), acylated (AG) and Unacylated ghrelin (UnAG). Plasma pro-inflammatory tumor necrosis factor alpha (TNFα) and anti-inflammatory interleukin-10 (IL-10) were also measured since changes in inflammation may contribute to UnAG activities. RESULTS: CR reduced BMI and increased insulin sensitivity (p < 0.05). TotalG and UnAG but not AG increased in CR but not in Control (p < 0.05). Il-10 and IL-10/TNFα ratio also increased in CR (p < 0.05). Changes in UnAG were positively associated with changes in AUCg in all subjects (n = 20; p < 0.01) also after adjustment for treatment and changes in BMI and cytokines. CONCLUSIONS: Caloric restriction modifies circulating ghrelin profile with selective increase in unacylated hormone in obese individuals. The current study supports the hypothesis that higher unacylated ghrelin contributes to improvements in insulin sensitivity following diet-induced weight loss in human obesity.
BACKGROUND & AIMS: Unacylated ghrelin (UnAG) modulates insulin sensitivity. Low plasma UnAG occurs in obesity and potentially contributes to obesity-associated insulin resistance. We hypothesized that improvements in insulin sensitivity in obese people induced by moderate caloric restriction (CR) may be paralleled and at least in part explained by concurrent increases in UnAG levels. METHODS: 20 general community obese people were randomly assigned to 16-week CR (n = 11) or control diet (n = 9). We investigated the impact of CR on the interaction between insulin sensitivity changes [area under the curve (AUCg) of glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamp] and plasma total (TotalG), acylated (AG) and Unacylated ghrelin (UnAG). Plasma pro-inflammatory tumor necrosis factor alpha (TNFα) and anti-inflammatory interleukin-10 (IL-10) were also measured since changes in inflammation may contribute to UnAG activities. RESULTS: CR reduced BMI and increased insulin sensitivity (p < 0.05). TotalG and UnAG but not AG increased in CR but not in Control (p < 0.05). Il-10 and IL-10/TNFα ratio also increased in CR (p < 0.05). Changes in UnAG were positively associated with changes in AUCg in all subjects (n = 20; p < 0.01) also after adjustment for treatment and changes in BMI and cytokines. CONCLUSIONS: Caloric restriction modifies circulating ghrelin profile with selective increase in unacylated hormone in obese individuals. The current study supports the hypothesis that higher unacylated ghrelin contributes to improvements in insulin sensitivity following diet-induced weight loss in human obesity.
Authors: A Benso; D H St-Pierre; F Prodam; E Gramaglia; R Granata; A J van der Lely; E Ghigo; F Broglio Journal: Eur J Endocrinol Date: 2012-02-29 Impact factor: 6.664
Authors: Nuria Barbarroja; Rosario López-Pedrera; Maria Dolores Mayas; Eduardo García-Fuentes; Lourdes Garrido-Sánchez; M Macías-González; Rajaa El Bekay; Antonio Vidal-Puig; Francisco J Tinahones Journal: Biochem J Date: 2010-08-15 Impact factor: 3.857
Authors: Patric J D Delhanty; Yuxiang Sun; Jenny A Visser; Anke van Kerkwijk; Martin Huisman; Wilfred F J van Ijcken; Sigrid Swagemakers; Roy G Smith; Axel P N Themmen; Aart-Jan van der Lely Journal: PLoS One Date: 2010-07-26 Impact factor: 3.240
Authors: Frederico G S Toledo; Elizabeth V Menshikova; Koichiro Azuma; Zofia Radiková; Carol A Kelley; Vladimir B Ritov; David E Kelley Journal: Diabetes Date: 2008-02-05 Impact factor: 9.461
Authors: T D Müller; R Nogueiras; M L Andermann; Z B Andrews; S D Anker; J Argente; R L Batterham; S C Benoit; C Y Bowers; F Broglio; F F Casanueva; D D'Alessio; I Depoortere; A Geliebter; E Ghigo; P A Cole; M Cowley; D E Cummings; A Dagher; S Diano; S L Dickson; C Diéguez; R Granata; H J Grill; K Grove; K M Habegger; K Heppner; M L Heiman; L Holsen; B Holst; A Inui; J O Jansson; H Kirchner; M Korbonits; B Laferrère; C W LeRoux; M Lopez; S Morin; M Nakazato; R Nass; D Perez-Tilve; P T Pfluger; T W Schwartz; R J Seeley; M Sleeman; Y Sun; L Sussel; J Tong; M O Thorner; A J van der Lely; L H T van der Ploeg; J M Zigman; M Kojima; K Kangawa; R G Smith; T Horvath; M H Tschöp Journal: Mol Metab Date: 2015-03-21 Impact factor: 7.422
Authors: Henriette Kirchner; Jesus A Gutierrez; Patricia J Solenberg; Paul T Pfluger; Traci A Czyzyk; Jill A Willency; Annette Schürmann; Hans-Georg Joost; Ronald J Jandacek; John E Hale; Mark L Heiman; Matthias H Tschöp Journal: Nat Med Date: 2009-06-05 Impact factor: 53.440