Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Pathophysiological regula… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Pathophysiological regulation of white adipocyte exocytosis of different adiponectin molecular forms

Doktorsavhandling
Författare Musovic Saliha
Datum för examination 2019-03-29
ISBN 978-91-7833-309-7
Förlag Göteborgs universitet
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Språk en
Länkar hdl.handle.net/2077/58489
Ämnesord White adipocytes, adiponectin exocytosis/secretion, health and metabolic disease
Ämneskategorier Fysiologi

Sammanfattning

In this thesis we have identified mechanisms involved in the exocytosis of different adiponectin molecular forms in health and in metabolic disease. We have also studied similarities and differences in depot-specific adipocyte adiponectin release. In paper I we show that the physiological regulation of subcutaneous white adipocyte adiponectin exocytosis involves β3 adrenergic receptors (β3ARs) and Exchange Protein directly Activated by cAMP isoform 1 (Epac1) signalling. Furthermore, we show that adiponectin secretion is disturbed in obesity/type 2 diabetes induced catecholamine resistance due to reduced abundance of the key proteins β3ARs and Epac1. This condition of catecholamine resistance is further associated with a ~50% reduction of circulating high-molecular weight (HMW) adiponectin. In paper II we show that β3AR-activation rapidly triggers the release of HMW adiponectin-containing vesicle whereas insulin induces release of smaller molecular forms, with delayed time-kinetics. We moreover demonstrate that both catecholamine-triggered exocytosis of HMW adiponectin and the insulin-induced secretion of smaller adiponectin forms is entirely diminished in adipocytes from obese/type 2 diabetic mice. The equivalent regulation of secretion of different adiponectin molecular forms by catecholamines and insulin was confirmed in human adipocytes, thus defining a novel role of β3ARs in human adipocyte function. In paper III we propose that adiponectin exocytosis is regulated by sympathetic nerve endings, co-releasing noradrenaline and ATP within the adipose tissue. Secretion measurements confirmed that noradrenaline (elevates cAMP), like adrenaline in paper I, triggers adiponectin exocytosis. Extracellular ATP was shown to augment the exocytotic process, largely due to its elevation of intracellular Ca2+. We also show that defect purinergic signalling together with reduced white adipose tissue noradrenaline content likely aggravates the catecholamine resistance observed in paper I and II. Finally we describe regulation of mouse visceral adipocyte adiponectin secretion in paper IV. As demonstrated in subcutaneous adipocytes (paper I-III), visceral adipocyte adiponectin secretion is also stimulated by activation of β3AR and Epac1. In obese/diabetic conditions, visceral adipocytes are likewise unresponsive to stimulation with catecholamines, but the underlying molecular defect does not involve reduced levels of neither β3AR nor Epac1, thus differing from observations in subcutaneous adipocytes. In conclusion, our results suggest that secretory defects in obesity/type 2 diabetes, attributed to catecholamine resistance, underlie the reduced levels of HMW adiponectin in metabolic disease.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?