scholarly journals Hypothalamic orexin A expression and the involvement of AMPK and PPAR-gamma signalling in energy restricted dairy cows

2011 ◽  
Vol 54 (6) ◽  
pp. 567-579 ◽  
Author(s):  
B. Kuhla ◽  
S. Görs ◽  
C. C. Metges

Abstract. A number of circuits controlling feed intake have been identified in rodents in which circulating dietary metabolites are detected by the brainstem and the hypothalamus converting these input signals to anorexic responses. Dietary metabolites used by dairy cows, however, are not identical with those of rodents calling for the elucidation of feedingrelated pathways in ruminants. In the present study we examined potentially relevant plasma metabolites and hypothalamic signalling pathways in ad libitum and restrictively fed early lactating dairy cows. 60 h feed energy restriction led to significantly increased non-esterified fatty acid (NEFA), Gln, Gly, His, and 3-Me-histine but decreased Asp, Asn, beta-Ala, Tyr, and Trp concentrations. In immunohistochemical studies, we found that feed energy restriction is associated with elevated numbers of parvocellular but not magnocellular orexin A neurons in the lateral, dorsomedial and posterior hypothalamic area. In parvocellular orexin A neurons we determined complete colocalisation with cFOS in energy restricted cows. In the majority of orexin A neurons we further found colocalisation with activated adenosine monophosphate activated kinase (AMPK) as well as with peroxisome proliferator-activated receptor-gamma (PPARγ). Feed restriction also induced activation (phosphorylation) of AMPK and increased expression of PPARγ when Western Blots were normalized to β-actin. These results suggest that orexin A associated with AMPK and PPARγ signalling is involved in the control of energy homeostasis of dairy cows.

2013 ◽  
Vol 394 (7) ◽  
pp. 865-870 ◽  
Author(s):  
Hany A. Omar ◽  
Samir A. Salama ◽  
El-Shaimaa A. Arafa ◽  
Jing-Ru Weng

Abstract Distinct metabolic strategies used by cancer cells to gain growth advantages, such as shifting from oxidative phosphorylation to glycolysis, constitute a basis for their selective targeting as a novel approach for cancer therapy. Thiazolidinediones (TZDs) are ligands for the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and they are clinically used as oral hypoglycemic agents. Accumulating evidence suggests that the ability of TZDs to suppress cancer cell proliferation through the interplay between apoptosis and autophagy was, at least in part, mediated through PPARγ-independent mechanisms. This review highlights recent advances in the pharmacological exploitation of the PPARγ-independent anticancer effects of TZDs to develop novel agents targeting tumor metabolism, including glucose transporter inhibitors and adenosine monophosphate-activated protein kinase, which have translational potential as cancer therapeutic agents.


Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 166
Author(s):  
Wonkyoung Cho ◽  
SeoYeon Kim ◽  
Myeongsook Jeong ◽  
Young Mi Park

Adipogenesis is a crucial cellular process that contributes to the expansion of adipose tissue in obesity. Shockwaves are mechanical stimuli that transmit signals to cause biological responses. The purpose of this study is to evaluate the effects of shockwaves on adipogenesis. We treated 3T3L-1 cells and human primary preadipocytes for differentiation with or without shockwaves. Western blots and quantitative real-time reverse transcriptase PCR (qRT-PCR) for adipocyte markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPα) were performed. Extracellular adenosine triphosphate (ATP) and intracellular cyclic adenosine monophosphate (cAMP) levels, which are known to affect adipocyte differentiation, were measured. Shockwave treatment decreased intracellular lipid droplet accumulation in primary human preadipocytes and 3T3-L1 cells after 11–12 days of differentiation. Levels of key adipogenic transcriptional factors PPARγ and/or C/EBPα were lower in shockwave-treated human primary preadipocytes and 3T3L-1 cells after 12–13 days of differentiation than in shockwave-untreated cells. Shockwave treatment induced release of extracellular ATP from preadipocytes and decreased intracellular cAMP levels. Shockwave-treated preadipocytes showed a higher level of β-catenin and less PPARγ expression than shockwave-untreated cells. Supplementation with 8-bromo-cAMP analog after shockwave treatment rescued adipocyte differentiation by preventing the effect of shockwaves on β-catenin, Wnt10b mRNA, and PPARγ expression. Low-energy shockwaves suppressed adipocyte differentiation by decreasing PPARγ. Our study suggests an insight into potential uses of shockwave-treatment for obesity.


Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.


Author(s):  
Nesibe Akyürek ◽  
Zehra Aycan ◽  
Semra Çetinkaya ◽  
Ömer Akyürek ◽  
Sebahat Yilmaz Ağladioğlu ◽  
...  

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.


2003 ◽  
Vol 10 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Ikuo Inoue ◽  
Kenji Hayashi ◽  
Fumiharu Yagasaki ◽  
Koh-ichi Nakamura ◽  
Toshiyuki Matsunaga ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5957
Author(s):  
Syed Amir Ashraf ◽  
Abd Elmoneim O. Elkhalifa ◽  
Khalid Mehmood ◽  
Mohd Adnan ◽  
Mushtaq Ahmad Khan ◽  
...  

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.


PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-19 ◽  
Author(s):  
Cadence E. Minge ◽  
Rebecca L. Robker ◽  
Robert J. Norman

Peroxisome proliferator-activated receptor gamma (PPARG) regulates cellular functions such as adipogenesis and immune cell activation. However, new information has indicated additional roles of PPARG directing the cyclic changes that occur within ovarian tissue of female mammals, including those that facilitate the release of oocytes each estrous cycle. In addition to ovarian PPARG expression and function, many PPARG actions within adipocytes and macrophages have additional direct and indirect implications for ovarian function and female fertility. This encompasses the regulation of lipid uptake and transport, insulin sensitivity, glucose metabolism, and the regulation of inflammatory mediator synthesis and release. This review discusses the developing links between PPARG activity and female reproductive function, and highlights several mechanisms that may facilitate such a relationship.


2016 ◽  
Vol 56 (7) ◽  
pp. 1185
Author(s):  
F. T. Fahri ◽  
I. J. Clarke ◽  
D. W. Pethick ◽  
R. D. Warner ◽  
F. R. Dunshea

Thiazolidinediones (TZD) are synthetic orally active peroxisome proliferator-activated receptor γ ligands used in the treatment of diabetes mellitus. The peroxisome proliferator-activated receptor γ gene plays an important role in regulating fat cell development, energy balance, and lipid metabolism in adipose and skeletal muscle tissue. There is interest in pharmacologic or nutritional means that may complement genetic techniques to improve growth and carcass composition of lambs and the major aim of the present study was to determine whether TZD impact on growth performance and meat quality of growing lambs. An initial study with four cross-bred lambs confirmed that rosiglitazone maleate is absorbed after oral dosing for 7 days. A second study was conducted with 30 cross-bred lambs to investigate the effects of sex (ewe vs wether) and dose of orally administered rosiglitazone maleate (0, 8 and 24 mg/day) for 55 days on growth performance, body composition, plasma metabolites and insulin and meat quality. Feed intake tended to increase linearly with dose of TZD (1521, 1816 and 1878 g/day for 0, 8 and 24 mg/day, P = 0.07) over the entire study, and particularly during the second half of the study (P < 0.05). There were both linear (P = 0.05) and quadratic (P = 0.04) responses in average daily gain to TZD (215, 270 and 261 g/day) with the quadratic response being most pronounced over the second half of the study (P = 0.004). As a result of the increased feed intake back fat (9.4, 11.1 and 13.5 mm, P < 0.001) and carcass fat (27.5%, 29.2% and 30.1%, P = 0.05) increased linearly with dose of TZD. However, there was no effect of TZD on internal fat depots. Plasma non-esterified acid concentrations increased linearly (0.37, 0.39 and 0.41 mM, P = 0.01) whereas plasma insulin concentrations (23.2, 26.9 and 20.9 mU/L, P = 0.05) and the homeostatic model assessment (6.82, 7.73 and 5.98, P = 0.05) exhibited quadratic responses to TZD. There were no significant effects of TZD on muscle pH, temperature or colour although muscle pH was higher at any temperature in ewes (+ 0.05 of a pH unit, P = 0.036) than in wethers. In conclusion, these data confirm that rosiglitazone maleate was rapidly absorbed from the digestive tract of growing ruminant lambs and was metabolically active. Oral TZD treatment appeared to mitigate against the inhibitory effect of carcass fatness on feed intake but the additional energy consumed was in turn deposited as fat.


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