scholarly journals Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity

2019 ◽  
Vol 8 (3) ◽  
pp. 203-216 ◽  
Author(s):  
Anna C Simcocks ◽  
Kayte A Jenkin ◽  
Lannie O’Keefe ◽  
Chrishan S Samuel ◽  
Michael L Mathai ◽  
...  

Atypical cannabinoid compounds O-1602 and O-1918 are ligands for the putative cannabinoid receptors G protein-coupled receptor 55 and G protein-coupled receptor 18. The role of O-1602 and O-1918 in attenuating obesity and obesity-related pathologies is unknown. Therefore, we aimed to determine the role that either compound had on body weight and body composition, renal and hepatic function in diet-induced obesity. Male Sprague–Dawley rats were fed a high-fat diet (40% digestible energy from lipids) or a standard chow diet for 10 weeks. In a separate cohort, male Sprague–Dawley rats were fed a high-fat diet for 9 weeks and then injected daily with 5 mg/kg O-1602, 1 mg/kg O-1918 or vehicle (0.9% saline/0.75% Tween 80) for a further 6 weeks. Our data demonstrated that high-fat feeding upregulates whole kidney G protein receptor 55 expression. In diet-induced obesity, we also demonstrated O-1602 reduces body weight, body fat and improves albuminuria. Despite this, treatment with O-1602 resulted in gross morphological changes in the liver and kidney. Treatment with O-1918 improved albuminuria, but did not alter body weight or fat composition. In addition, treatment with O-1918 also upregulated circulation of pro-inflammatory cytokines including IL-1α, IL-2, IL-17α, IL-18 and RANTES as well as plasma AST. Thus O-1602 and O-1918 appear not to be suitable treatments for obesity and related comorbidities, due to their effects on organ morphology and pro-inflammatory signaling in obesity.

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
O. Merino ◽  
R. Sánchez ◽  
B. M. Gregorio ◽  
F. J. Sampaio ◽  
J. Risopatrón

Obesity has adverse effects on male fertility and usually is diagnosed with a prevalence of vitamin D deficiency (VD-). Discussion on the impact of obesity/VD- on sperm function has been limited. This study analyzed the effects of diet-induced obesity/VD- on viability and plasma membrane integrity (PMI), superoxide anion (O2-) level, and DNA fragmentation (DNAfrag) in sperm Sprague-Dawley rats. The males were randomized into four groups and fed for a period of 12 weeks: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+), and G4: high-fat diet without vitamin D (HF/VD-). Sperm function parameters were analyzed by flow cytometry. PMI percentages and O2- levels were not affected by any of the diets. DNA fragmentation was increasing significantly (p<0.05) in the spermatozoa of animals with diets vitamin D deficient (G2) and diet-induced obesity (G4). Our results allow us to point out that diet-induced obesity and VD- produce greater damage in DNA sperm of rats. The use of nutraceuticals containing vitamin D could be reducing the risk of fragmentation of DNA in spermatozoa.


2017 ◽  
Vol 28 (3) ◽  
pp. 748-759 ◽  
Author(s):  
Dominika Stygar ◽  
Tomasz Sawczyn ◽  
Bronisława Skrzep-Poloczek ◽  
Aleksander J. Owczarek ◽  
Natalia Matysiak ◽  
...  

2006 ◽  
Vol 76 (5) ◽  
pp. 271-279 ◽  
Author(s):  
Pérez de Heredia ◽  
Garaulet ◽  
Puy Portillo ◽  
Zamora

Susceptibility to dietary obesity was studied in Wistar and Sprague-Dawley rats submitted to different high-energy diets. Experiment 1: female Sprague-Dawley rats were fed chow (n = 6) or a high-fat diet (n = 12) for 22 weeks. Experiment 2: Wistar rats were fed chow or a high-fat diet, and Sprague-Dawley rats were given chow, high-fat, sweet condensed milk, or cafeteria diets, for eight weeks (6 animals per group). Food intake and body weight were recorded weekly. Adipose tissue was collected from periovarian, mesenteric, and subcutaneous regions and adipocytes were isolated and measured. Both strains showed similar energy intake and body weight gain. Wistar rats reached greater final body fat contents than Sprague-Dawley rats, regardless of the type of diet. However, resistance to dietary obesity was found in 100% of cases in both experiments. None of the diets succeeded in increasing body fat accumulation when compared to control groups. All adipose tissue locations were equally unaffected, with periovarian fat cells being larger than those in mesenteric and subcutaneous regions in all the groups. In view of the strong resistance to obesity observed in rats, it should be important for researchers to transmit the difficulties of inducing dietary obesity in these animals, in order to prevent bias in science interpretation.


Peptides ◽  
2019 ◽  
Vol 115 ◽  
pp. 75-84
Author(s):  
Tomasz Sawczyn ◽  
Dominika Stygar ◽  
Katarzyna Nabrdalik ◽  
Michał Kukla ◽  
Bronisława Skrzep-Poloczek ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Brian Dake ◽  
Mark A. Yorek

The objective of this study was to determine the effect of AVE7688, a drug that inhibits both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activity, on neural and vascular defects caused by diet induced obesity (DIO). Rats at 12 weeks of age were fed a standard or high fat diet with or without AVE7688 for 24 weeks. DIO rats had impaired glucose tolerance and developed sensory neuropathy. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased in epineurial arterioles of DIO rats. Rats fed a high fat diet containing AVE7688 did not become obese and vascular and sensory nerve dysfunction and impaired glucose tolerance were improved. DIO is associated with increased expression of NEP in epineurial arterioles. NEP degrades vasoactive peptides which may explain the decrease in neurovascular function in DIO.


2020 ◽  
Author(s):  
Neng Tine Kartinah ◽  
Nisa Komara ◽  
Nuraini Diah Noviati ◽  
Syarifah Dewi ◽  
Sophie Yolanda ◽  
...  

Abstract Background Obesity is a cause of Fgf21 resistance, which affects the browning and thermogenesis process of the adipose tissue. Decreased receptor expression is influenced by microRNA 34a (miR-34a), whose expression is increased in obesity. While Fgf21-based therapies have been widely investigated, the potential activity of Hibiscus sabdariffa Linn extract (HSE) against Fgf21 resistance is unknown. This study aims to determine the effects of HSE on the expression of miR-34a and Fgf21 receptors in white adipose tissue. Methods This experimental study used 24 male Sprague-Dawley rats and divided into four groups: Control (N); diet-induced-obesity rats (DIO); DIO rats with HSE 200 mg/kgBW/day and DIO rats with HSE 400 mg/kgBW/day. Rats were fed a high-fat diet for 17 weeks. HSE was administered daily for five weeks. The administration of HSE 400 mg/kg BW/day resulted in the equivalent expression of miR-34a to that of the control (p > 0.05). Results Fgfr1 receptor expression was also similar to controls (p > 0.05). Beta-klotho expression was significantly lower than that of Control (p < 0.05) but equivalent to that of DIO rats (p < 0.05). Conclusions H. sabdariffa has the potential to reduce Fgf21 resistance in DIO rats through the suppression of miR-34a expression and an increase in the number of Fgfr1 and beta-klotho receptors in adipose tissue.


2018 ◽  
Vol 29 (5) ◽  
pp. 553-563 ◽  
Author(s):  
Shakthi R.K. Devan ◽  
Surendar Arumugam ◽  
Ganesh Shankar ◽  
Suresh Poosala

AbstractBackgroundThe prevalence of obesity is reported to be increasing owing to the high intake of dietary fat and is a predisposing risk factor with associated complex metabolic syndromes in the human population. Preclinical rodent models play a pivotal role in understanding the pathogenesis of obesity and development of new treatment strategies for humans. High-fat-diet (HFD)-induced rodents are used for chronic obesity models owing to their quick adaptation to high-fat diets and rapid body weight gain and different rats (Wistar Sprague-Dawley and Lewis) have been used by various researchers. However, the selection of appropriate stock contributes to the translation of clinically linked disease phenotypes to preclinical animal models.MethodsThe study was conducted using two commonly used rat stocks Hsd:Sprague-Dawley (SD) and Crl:Charles River (CD) to develop a chronic high-fat-diet-induced obesity model (DIO) to explore the underlying mechanisms of obesity and its utilization in drug discovery and development during preclinical stages. In addition two high-fat diets of different composition were evaluated (D12327; 40% kcal fat and D12492; 60% kcal fat) for their potential to induce obesity using these two stocks.ResultsA differential sensitivity to HFD was observed in body weight gain fat mass composition and obesity-linked symptoms such as impaired glucose tolerance insulin and leptin levels. The comparative research findings of Hsd:SD and Crl:CD rat stocks suggested that Crl:CD rats are more prone to diet-induced obesity and its associated complications.ConclusionsCrl:CD rats were found to be a suitable model for obesity over Hsd:SD when considering the important hallmarks of metabolic disorders that may be utilized for obesity-related research.


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