leptin and guanylin

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

Topics: Adaptation, Physiological; Adiponectin; Androgens; Animals; Asthma; Bronchodilator Agents; Dehydroepiandrosterone; Epinephrine; Estrogens; Female; Fibrin; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Glucocorticoids; Humans; Insulin; Leptin; Lung; Male; Muscle Contraction; Muscle, Smooth; Natriuretic Peptides; Progesterone; Respiratory Physiological Phenomena; Respiratory System; Theophylline; Thyroid Hormones; Urokinase-Type Plasminogen Activator

The gastrointestinal tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural, and nutrient signals emanating from the gastrointestinal tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacologic and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing body weight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 highlights the therapeutic potential of gut-derived signals acting via nonphysiologic mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage gastrointestinal signals in order to treat obesity.

Topics: Animals; Apolipoproteins A; Calcium-Binding Proteins; Cholecystokinin; DNA-Binding Proteins; Eating; Energy Metabolism; Enteroendocrine Cells; Gastrointestinal Hormones; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Leptin; Natriuretic Peptides; Nerve Tissue Proteins; Neurons, Afferent; Neurotensin; Nucleobindins; Obesity; Oxyntomodulin; Peptide YY; Receptors, G-Protein-Coupled