Association of serum leptin with hypoventilation in human obesity

Phipps, P. R.; Starritt, E.; Caterson, I.; Grunstein, R. R.
January 2002
Thorax;Jan2002, Vol. 57 Issue 1, p75
Academic Journal
Background: Leptin is a protein hormone produced by fat cells of mammals. It acts within the hypothalamus via a specific receptor to reduce appetite and increase energy expenditure. Plasma leptin levels correlate closely with total body fat mass operating via a central feedback mechanism. In human obesity serum leptin levels are up to four times higher than in lean subjects, indicating a failure of the feed- back loop and central leptin resistance. In leptin deficient obese mice (ob/ob mice) leptin infusion reverses hypoventilation. It was hypothesised that a relative deficiency in CNS leptin, indicated by high circulating leptin levels, may be implicated in the pathogenesis of obesity hypoventilation syndrome (OHS). Methods: Fasting morning leptin levels were measured in obese and non-obese patients with and without daytime hypercapnia (n=56). Sleep studies, anthropometric data, spirometric parameters, and awake arterial blood gas tensions were measured in each patient. Results: In the whole group serum leptin levels correlated closely with % body fat (r=0.77). Obese hypercapnic patients (mean (SD) % body fat 43.8 (6.0)%) had higher fasting serum leptin levels than eucapnic patients (mean % body fat 40.8 (6.2)%), with mean (SD) leptin levels of 39.1 (17.9) and 21 .4 (11 .4) ng/ml, respectively (p<0.005). Serum leptin (odds ratio (OR) 1.12, 95% Cl 1.03 to 1 .22) was a better predictor than % body fat (OR 0.92, 95% CI 0.76 to 1 .1) for the presence of hypercapnia. Conclusions: Hyperleptinaemia is associated with hypercapnic respiratory failure in obesity. Treatment with leptin or its analogues may have a role in OHS provided central leptin resistance can be overcome.


Related Articles

  • Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism. Zhou, Xun; Gomez-Smith, Mariana; Qin, Zhaohong; Duquette, Philippe; Cardenas-Blanco, Arturo; Rai, Punarpreet; Harper, Mary-Ellen; Tsai, Eve; Anisman, Hymie; Chen, Hsiao-Huei // Cellular & Molecular Life Sciences;Mar2012, Vol. 69 Issue 5, p819 

    The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we...

  • Leptin Is a Potent Chemoattractant for Monocytes and Promotes Macrophage Accumulation in White Adipose Tissue. Gruen, Marnie L.; Surmi, Bonnie K.; Atkinson, Robin D.; Hasty, Alyssa H. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA460 

    The growing world-wide obesity epidemic is frequently linked to hyperlipidemia, inflammation, and insulin resistance leading to increased risk of diabetes and cardiovascular disease. Macrophages have been shown to infiltrate white adipose tissue (WAT) in obese mice and humans promoting...

  • FGF21 Promotes Metabolic Homeostasis via White Adipose and Leptin in Mice. Véniant, Murielle M.; Hale, Clarence; Helmering, Joan; Chen, Michelle M.; Stanislaus, Shanaka; Busby, Jim; Vonderfecht, Steven; Jing Xu; Lloyd, David J. // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    Fibroblast growth factor 21 (FGF21) is a potent metabolic regulator, and pharmacological administration elicits glucose and lipid lowering responses in mammals. To delineate if adipose tissue is the predominant organ responsible for anti-diabetic effects of FGF21, we treated mice with reduced...

  • Induction of TDO2 and IDO2 in Liver by High-Fat Feeding in Mice: Discrepancies with Human Obesity. Poulain-Godefroy, Odile; Eury, Elodie; Leloire, Audrey; Hennart, Benjamin; Guillemin, Gilles J.; Allorge, Delphine; Froguel, Philippe // International Journal of Tryptophan Research;2013 Supplement, Issue 6, p29 

    Low-grade and chronic inflammation is elicited in white adipose tissue in human obesity. The presence of inflammatory molecules leads to an increased tryptophan catabolism through the induction of indoleamine-2,3-dioxygenase-1 (IDO1). In order to characterize the mechanisms underlying this...

  • The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells. Cahan, Patrick; Li, Yedda; Izumi, Masayo; Graubert, Timothy A // Nature Genetics;Apr2009, Vol. 41 Issue 4, p430 

    The extent to which differences in germline DNA copy number contribute to natural phenotypic variation is unknown. We analyzed the copy number content of the mouse genome to sub–10-kb resolution. We identified over 1,300 copy number variant regions (CNVRs), most of which are <10 kb in...

  • Diabetes genes identified by genome-wide association studies are regulated in mice by nutritional factors in metabolically relevant tissues and by glucose concentrations in islets. Ho, Maggie M.; Yoganathan, Piriya; Kwan Yi Chu; Karunakaran, Subashini; Johnson, James D.; Clee, Susanne M. // BMC Genetics;2013, Vol. 14 Issue 1, p1 

    Background: Genome-wide association studies (GWAS) have recently identified many new genetic variants associated with the development of type 2 diabetes. Many of these variants are in introns of known genes or between known genes, suggesting they affect the expression of these genes. The...

  • Thyroid hormones: igniting brown fat via the brain. Cannon, Barbara; Nedergaard, Jan // Nature Medicine;Sep2010, Vol. 16 Issue 9, p965 

    The article discusses the thyroid thermogenesis process. It relates the study of M. Lopez and colleagues which examines the effects of thyroid hormone in hypothalamus of mice, a part of the brain controlling physiological functions such as eating, wherein the result shows the whole-body effects...

  • In Neurons, Sirtuin1 Can Help Prevent Diet-Induced Obesity. Breindl, Anette // BioWorld Today;7/8/2010, Vol. 21 Issue 130, p1 

    The article discusses the possible role of sirtuins, specifically SIRT1 in POMC-containing neurons in the hypothalamus, in the control of body weight. Laboratory experiments showed that mice with and without the SIRT1 gene exhibited the same appetite, but when put on a high-fat diet, females...

  • NPY Neuron-Specific Y2 Receptors Regulate Adipose Tissue and Trabecular Bone but Not Cortical Bone Homeostasis in Mice. Yan-Chuan Shi; Shu Lin; Wong, Iris P. L.; Baldock, Paul A.; Aljanova, Aygul; Enriquez, Ronaldo F.; Castillo, Lesley; Mitchell, Natalie F.; Ji-Ming Ye; Lei Zhang; Macia, Laurence; Yulyaningsih, Ernie; Nguyen, Amy D.; Riepler, Sabrina J.; Herzog, Herbert; Sainsbury, Amanda // PLoS ONE;2010, Vol. 5 Issue 6, p1 

    Background: Y2 receptor signalling is known to be important in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone physiology. Y2 receptors are located post-synaptically as well as acting as auto receptors on NPYexpressing neurons, and the different roles of these two...


Read the Article


Sign out of this library

Other Topics