Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans.

Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 +/- 0.8 pg.mL-1; hypoxia, 7.7 +/- 1.5 pg.mL-1; p < 0.05; range, -16% to 190%), no change in the average GLP-1 response to hypoxia, and only a small trend toward an increase in GLP-1 levels 40 min postmeal (fasting, 15.7 +/- 0.9 vs 15.9 +/- 0.7 pmol.L-1; 20 min postmeal, 21.7 +/- 0.9 vs 21.8 +/- 1.2 pmol.L-1; 40 min postmeal, 19.5 +/- 1.2 vs. 21.0 +/- 1.2 pmol.L-1 for normoxia and hypoxia, respectively; p > 0.05 normoxia vs hypoxia). There was a correlation between SaO2 and leptin after the 17 h exposure (r = 0.45; p < 0.05), but no relation between SaO2 and GLP-1. These data confirm that leptin increases with hypoxic exposure in humans. Further study is needed to determine the influence of hypoxia and altitude on GLP-1 levels.

[1]  H. Gehring,et al.  Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions , 2009, International journal of endocrinology.

[2]  E. Bojanowska,et al.  Interactions between leptin and exendin-4, a glucagon-like peptide-1 agonist, in the regulation of food intake in the rat. , 2007, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[3]  A. Bigard,et al.  Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia. , 2006, American journal of physiology. Endocrinology and metabolism.

[4]  P. K. Banerjee,et al.  Ghrelin and leptin levels of sojourners and acclimatized lowlanders at high altitude , 2005, Nutritional neuroscience.

[5]  W. Cupples,et al.  Physiological regulation of food intake. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[6]  S. Jackson,et al.  Evidence against redox regulation of energy homoeostasis in humans at high altitude. , 2004 .

[7]  C. Deacon.  Circulation and Degradation of GIP and GLP-1 , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[8]  C. Beglinger,et al.  Interaction between GLP-1 and CCK-33 in inhibiting food intake and appetite in men. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  A. Cabrera de León,et al.  Leptin and altitude in the cardiovascular diseases. , 2004, Obesity research.

[10]  R. L. Richardson,et al.  Adipose tissue angiogenesis. , 2004, Journal of animal science.

[11]  P. Brubaker,et al.  Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. , 2003, Canadian journal of physiology and pharmacology.

[12]  P. Brubaker,et al.  Role of leptin in the regulation of glucagon-like peptide-1 secretion. , 2003, Diabetes.

[13]  C. Magnan,et al.  Leptin receptor-deficient obese Zucker rats reduce their food intake in response to a systemic supply of calories from glucose. , 2003, Diabetes.

[14]  J. Pouysségur,et al.  Hypoxia-inducible Factor 1 Transactivates the Human Leptin Gene Promoter* , 2002, The Journal of Biological Chemistry.

[15]  T. Issad,et al.  Leptin is a hypoxia-inducible gene. , 2002, Obesity research.

[16]  T. Issad,et al.  Hypoxia increases leptin expression in human PAZ6 adipose cells , 2002, Diabetologia.

[17]  D. Drucker.  Biological actions and therapeutic potential of the glucagon-like peptides. , 2002, Gastroenterology.

[18]  T. Yasumasu,et al.  Hypoxia inhibits leptin production by cultured rat adipocytes. , 2002, Obesity research.

[19]  S. Hauguel-de Mouzon,et al.  Transcriptional effect of hypoxia on placental leptin , 2001, FEBS letters.

[20]  J. Biollaz,et al.  Influence of hypobaric hypoxia on leptin levels in men , 2000, International Journal of Obesity.

[21]  C. Bailey.  Potential new treatments for type 2 diabetes. , 2000, Trends in pharmacological sciences.

[22]  Clifford B. Saper,et al.  Leptin Regulation of Neuroendocrine Systems , 2000, Frontiers in Neuroendocrinology.

[23]  D. Drucker,et al.  Synthesis, secretion and biological actions of the glucagon‐like peptides , 2000, Pediatric diabetes.

[24]  M. Westerterp-Plantenga.  Effects of extreme environments on food intake in human subjects , 1999, Proceedings of the Nutrition Society.

[25]  M. Westerterp-Plantenga,et al.  Appetite at "high altitude" [Operation Everest III (Comex-'97)]: a simulated ascent of Mount Everest. , 1999, Journal of applied physiology.

[26]  J. Auwerx,et al.  Leptin , 1998, The Lancet.

[27]  M. Gassmann,et al.  Oxygen(es) and the hypoxia-inducible factor-1. , 1997, Biological chemistry.

[28]  J. Bittel,et al.  Evaluation of the Lake Louise acute mountain sickness scoring system in a hypobaric chamber. , 1995, Aviation, space, and environmental medicine.

[29]  M. Pelleymounter,et al.  Effects of the obese gene product on body weight regulation in ob/ob mice. , 1995, Science.

[30]  K. Westerterp,et al.  Energy balance at high altitude of 6,542 m. , 1994, Journal of applied physiology.

[31]  J. Holst,et al.  Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans , 1994, Diabetes.

[32]  S. Poulsen,et al.  Glucagonlike Peptide-I-(7–36)-Amide Receptors Only in Islets of Langerhans: Autoradiographic Survey of Extracerebral Tissues in Rats , 1991, Diabetes.

[33]  G. Coates,et al.  Operation Everest. II: Nutrition and body composition. , 1988, Journal of applied physiology.

[34]  J. Brozek.  Nutrition and body composition. , 1965, Borden's review of nutrition research.

[35]  E. Blázquez,et al.  Leptin but not neuropeptide Y up-regulated glucagon-like peptide 1 receptor expression in GT1-7 cells and rat hypothalamic slices. , 2008, Metabolism: clinical and experimental.

[36]  J. Holst,et al.  Effect of a high-protein breakfast on the postprandial ghrelin response 1 – 3 , 2006 .

[37]  Geoffrey C Gurtner,et al.  Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. , 2003, The American journal of pathology.

[38]  M. Tschöp,et al.  Weight loss at high altitude. , 2001, Advances in experimental medicine and biology.

[39]  J. Holst,et al.  Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. , 1999, Endocrinology.