Kopp, Christina: Regulation of adiponectin expression by trans-cinnamic acid and niacin in murine and bovine adipocytes in vitro. - Bonn, 2016. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-44053
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-44053,
author = {{Christina Kopp}},
title = {Regulation of adiponectin expression by trans-cinnamic acid and niacin in murine and bovine adipocytes in vitro},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2016,
month = jun,

note = {Adipose tissue secretes multiple metabolically important proteins known as adipokines, one of the most abundant is adiponectin (AdipoQ). Known as an important modulator of glucose and fat metabolism, adipoQ is a key regulator of insulin sensitivity and thereby takes part in protection against the development of obesity and type 2 diabetes. Dairy cows undergo various metabolic changes during the transition period. This period from late pregnancy to early lactation is crucial for the potential development of many diseases and metabolic disorders. Energy requirements increase due to the nutrient demand of the fetus and mammary gland and cannot be covered by feed intake only. The negative energy balance is characterized by increased lipolysis and reduced insulin sensitivity in peripheral tissues. Due to its insulin-sensitizing effect, AdipoQ is not only of great interest in humans, but also for dairy cows during the transition period. Hence, strategies to improve synthesis and secretion of AdipoQ are of major interest in various species. Cinnamon is known to exert several beneficial effects by improving insulin sensitivity and lipid profiles and to increase AdipoQ concentrations. In this thesis we focused on the barely explored cinnamon compound trans-cinnamic acid (tCA) as potential AdipoQ ameliorant. In addition, Niacin (NIA) is known to decrease lipolysis and plasma NEFA levels in lactating cows and to increase AdipoQ concentration in rodents and may therefore have the ability to emend the metabolic situation of dairy cows during the transition period via improving AdipoQ. Since nicotinic acid (NA), a compound of NIA, as well as tCA are both ligands of the G-protein-coupled receptor (GPR)109A, not only the effects on AdipoQ were of interest but also the signaling pathway. Therefore, this thesis aimed to investigate the effects of tCA on AdipoQ secretion in murine 3T3-L1 adipocytes and to evaluate the changes in AdipoQ secretion and mRNA abundance of selected genes after supplementation with NA in bovine adipocytes. In addition, the involvement of the GPR109A in the signaling pathway towards AdipoQ was examined. Therefore, the murine and bovine adipocytes were pre-incubated with pertussis toxin (PTX), an inhibitor of Gi/Go protein coupling. Treatment with tCA increased AdipoQ concentrations significantly, but incubation with PTX decreased AdipoQ secretion. By this study we identified tCA as an influencing variable on AdipoQ, indicating tCA as effective compound of cinnamon, with the capability to improve glucose and fat metabolism. Furthermore, an involvement of GPR signaling, induced by tCA, was shown. After establishing a bovine primary cell culture model, the potential effect of NA on AdipoQ was tested. Treatment with NA increased both AdipoQ concentrations and the mRNA abundance of GPR109A. Pre-incubation with PTX reduced the AdipoQ response to NA. The NA-stimulated AdipoQ secretion and of GPR109A mRNA expression in bovine adipocytes were suggestive for GPR signaling-dependent improved insulin sensitivity in dairy cows. In addition, in both studies PTX pre-incubation AdipoQ concentrations were significantly decreased, but remained increased when compared to non-treated adipocytes. These observations contrast other findings that observed no increase in AdipoQ secretion after stimulation with NA and PTX in rat adipocytes. Therefore, we suggest, in addition to GPR signaling-dependent pathways, a GPR independent pathway in the regulation of AdipoQ secretion after stimulation with tCA and NA. This thesis identified two factors improving AdipoQ secretion in murine and bovine adipocytes. Furthermore, participation of GPR signaling as well as another GPR-independent,tCA/NA-induced pathway to stimulate AdipoQ was detected. These results may pave the way for further studies to understand and improve the metabolic changes during the transition period in bovine AT in vitro and may establish a basis for upcoming in vivo studies.},
url = {http://hdl.handle.net/20.500.11811/6619}

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