scholarly journals Propensity to endoplasmic reticulum stress in deer mouse fibroblasts predicts skin inflammation and body weight gain

2021 ◽  
Vol 14 (10) ◽  
Author(s):  
Youwen Zhang ◽  
Chang-uk Lim ◽  
Vitali Sikirzhytski ◽  
Asieh Naderi ◽  
Ioulia Chatzistamou ◽  
...  

ABSTRACT The unfolded protein response (UPR) is involved in the pathogenesis of metabolic disorders, yet whether variations in the UPR among individuals influence the propensity for metabolic disease remains unexplored. Using outbred deer mice as a model, we show that the intensity of UPR in fibroblasts isolated early in life predicts the extent of body weight gain after high-fat diet (HFD) administration. Contrary to those with intense UPR, animals with moderate UPR in fibroblasts and therefore displaying compromised stress resolution did not gain body weight but developed inflammation, especially in the skin, after HFD administration. Fibroblasts emerged as potent modifiers of this differential responsiveness to HFD, as indicated by the comparison of the UPR profiles of fibroblasts responding to fatty acids in vitro, by correlation analyses between UPR and proinflammatory cytokine-associated transcriptomes, and by BiP (also known as HSPA5) immunolocalization in skin lesions from animals receiving HFD. These results suggest that the UPR operates as a modifier of an individual's propensity for body weight gain in a manner that, at least in part, involves the regulation of an inflammatory response by skin fibroblasts. This article has an associated First Person interview with the first author of the paper.

Agriculture ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 93 ◽  
Author(s):  
Lilith Schrey ◽  
Nicole Kemper ◽  
Michaela Fels

The aim of this study was to analyse a novel group farrowing system (GH) concerning piglets’ behaviour, skin injuries and body weight gain, to test its animal friendliness. Skin injuries and weight gain were compared to piglets originating from conventional individual housing (IH) before and after weaning. The GH system had five farrowing pens without crates, a common area and an area only available for piglets. In total, 34 litters were studied. Four days after the GH-piglets had left the pens during lactation, the lesion score of piglets in GH was higher than in IH. However, piglets from the GH sustained fewer injuries after mixing at weaning, compared to the piglets from IH and had higher daily weight gains, during the early nursery phase. The common area in GH was intensively used for active behaviour, since standing/walking and playing were observed there, most frequently, whereas lying occurred most frequently inside the pens. Immediately after the piglets had left the pens in the GH, the piglets preferred proximity to the sow, compared to the pens where they were born. The GH system enabled social enrichment, offered increased space for activity and led to fewer skin lesions, after weaning; thus, potentially increasing animal welfare.


2021 ◽  
Author(s):  
Karunakaran Reddy Sankaran ◽  
Lokanatha Oruganti ◽  
Muni Swamy Ganjayi ◽  
Venkataramaiah Chintha ◽  
Muni Kesavulu Muppuru ◽  
...  

Abstract Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).


Author(s):  
Geke Aline Boer ◽  
Jenna Hunt ◽  
Maria Gabe ◽  
Johanne Windeløv ◽  
Alexander Sparre-Ulricht ◽  
...  

Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity but its exact role in these processes is unclear. Experimental approach We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomized mice during an 8-week treatment period. Key results mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor (GIPR) in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 hours in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomized HFD mice resulted in a reduction of body weight and fat mass. Conclusion and Implications mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomized mice. Our results support the development of GIP antagonists for the therapy of obesity.


2016 ◽  
Vol 7 (1) ◽  
pp. 35-44 ◽  
Author(s):  
S. Asghar ◽  
M. Arif ◽  
M. Nawaz ◽  
K. Muhammad ◽  
M.A. Ali ◽  
...  

Aim of the present study was to characterise and evaluate probiotic potential of lactobacilli isolated from indigenous poultry. Lactobacilli were isolated from poultry droppings and identified by genus specific polymerase chain reaction and 16S rRNA gene sequencing. Isolates were characterised in vitro by their ability to tolerate low pH and bile salts, phytase activity, antimicrobial activity, antibiotic susceptibility profile, and autoaggregation and coaggregation with poultry gut pathogens. In vivo evaluation of selected isolates was done by their effect on the body weight gain and immune response of broiler chicks. Total of 90, one-day old chicks, were randomly divided in 9 groups and given selected lactobacilli alone and in combinations (108 cfu/bird, daily) from day 7 to day 35. Body weight gain and humoral immune response to New Castle Disease Virus (NDV) vaccine were determined weekly. Three lactobacilli isolates (SMP52, SMP64 and SMP70) were selected as potentially probiotic bacteria on the basis of in vitro characterisation and identified as Lactobacillus crispatus, Lactobacillus casei and L. crispatus, respectively. Chicks supplemented with ‘SMP52’, ‘SMP64’, ‘SMP70’ and ‘SMP64+SMP70’ and a commercial probiotic product (Protexin) showed significantly higher mean weight gain per bird (1,584±35.2, 1,629±30.6, 1,668±34.7, 1,619±29.5 and 1,576±31.7 g/bird, respectively) as compared to negative control group (1,394±26.7 g/bird), on day 35. SMP 70 also showed significantly higher geometric mean titre against NDV vaccine at day 21 as compared to negative control. It is concluded that L. crispatus SMP52, L. casei SMP64 and L. crispatus SMP70 are potential probiotic candidates which alone or in different combinations may increase body weight of broilers.


2006 ◽  
Vol 189 (1) ◽  
pp. 147-154 ◽  
Author(s):  
G Tachas ◽  
S Lofthouse ◽  
C J Wraight ◽  
B F Baker ◽  
N B Sioufi ◽  
...  

Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-I, and there is a need for improved therapies. We have designed an optimised 2′-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.


1986 ◽  
Vol 251 (3) ◽  
pp. R433-R440 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
A. C. Sullivan

Diet-induced obesity (DIO) developed in 1-mo-old male Sprague-Dawley rats over an 8-wk period on a relatively high-fat (16%) high-calorie (4.6 kcal/g) diet (DIO diet). Percent carcass lipid (56%) and body weight gain (15%) were greater, whereas food intake was decreased over the first 3-5 wk in DIO diet-compared with chow-fed controls. Overall, 8-wk body weight gain (15%), percent carcass lipid (26%), and feed efficiency (15%) were greater, but food intake was not increased. Norepinephrine (NE) turnover rate, indicative of organ sympathetic activity, increased in interscapular brown adipose tissue (IBAT; 57-218%), heart (21-44%), and pancreas (25%) during the first 3 wk and remained elevated for the entire 8 wk. IBAT weight (51%) and in vitro lipolytic capacity (68%) increased by 1 wk and brown adipocyte size (43%) by 3 wk; IBAT thermogenic capacity (maximal NE-stimulated in vitro O2 consumption) increased by 5 wk (39%). Plasma insulin levels were similar in both diet groups over the entire 8-wk period. Why DIO diet-fed rats had increased metabolic efficiency is unknown, but activation of IBAT metabolism and thermogenesis failed to prevent the development of DIO.


2021 ◽  
Vol 19 (2) ◽  
pp. 91-99
Author(s):  
Amanda G. Elias ◽  
Julia S. da Silva ◽  
Rafaela L. Klein ◽  
Francieli U. I. Amaral ◽  
Marcelo D. Arbo ◽  
...  

Introduction: Nimesulide is a potent anti-inflammatorywith rapid and long-lasting effects, but also with a high riskof hepatotoxicity. Objective: This work aimed to preventnimesulide-induced hepatotoxicity through the associationof nimesulide with a hepatoprotective agent. Materials andMethods: First, we tested three hepatoprotective agents:N-acetylcysteine, L-carnitine, and Gingko biloba extract inan in vitro hepatic cell model. Both N-acetylcysteine and G.biloba showed promisor results. We selected N-acetylcysteineto continue the studies in an animal model. In vivo study wasperformed using male Wistar rats divided in 4 groups: control,nimesulide (100mg/kg/day), nimesulide (100mg/kg/day) +N-acetylcysteine (100mg/kg/day) and N-acetylcysteine alone(100mg/kg/day). Treatments were given by gavage, daily, for15 days. Results: Animals receiving nimesulide alone showedlower body weight gain compared to control. Body weightgain in the nimesulide + N-acetylcysteine group was higherthan nimesulide alone, evidencing lower toxicity. However,the body weight gain of the nimesulide + N-acetylcysteinegroup was still lower than the control animals. Animals treatedwith nimesulide alone presented an increased relative mass ofheart, liver, and spleen and significant hepatic damage seen inmicroscopy when compared to other groups. N-acetylcysteineco-administered with nimesulide prevented the increasedheart mass, but the same was not true with liver and spleen.Conclusions: This work evidence partial protection elicitedby the association of N-acetylcysteine and nimesulide againstnimesulide-induced hepatotoxicity.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Dong Hyun Kim ◽  
Morghan S Getty ◽  
David E Stec ◽  
Nader G Abraham

Introduction: Obesity or high fat diet (HF) are risk factors for the development of hypertension. We examined the hypothesis that targeting the vascular system with human heme oxygenase -1 (HO-1) may attenuate both vascular and adipocyte dysfunction in vivo and in vitro. Methods: Lentivirus (Lenti) construct expressing human HO-1 under the control of endothelium specific promoters VE-cadherin (VECAD-HO-1) and VECAD −GFP (control) were used to treat mice, using a bolus injection into the renal artery, and kept on a high fat diet for 26 weeks. Human HO-1 gene expression was sustained for 9 months. For in vitro studies, human EC were cultured with Lenti- VECAD-HO-1 and added to Lenti-VECAD-GFP or control. The conditioned media (CM) from ECs was harvested and 10% CM was added to adipogenic media to measure paracrine effect on adipogenesis in human Mesenchymal Stem Cells (MSCs) derived adipocytes. Signaling molecules were measured by western blot. Results: Lentiviral transduction with VECAD-HO-1 construct attenuated the increase in blood pressure (from 149.9 ± 2.4 to 118 ± 2.0 mmHg, p<0.01) and prevented body weight gain by 39% (p<0.05) in obese mice and increased plasma adiponectin (from 2.9 ± 0.2 to 6.5 ± 0.1 μg/ml, p<0.05). CM derived from EC lenti HO-1 decreased adipogenesis compared to control (from 17.0 ± 0.2 to 10.2 ± 0.1, p<0.05) and resulted in an increase of β-catenin and Wnt but a decrease in PPARγ (p<0.05). These beneficial effects were reversed by treating the cell with SnMP, an inhibitor of HO activity (p<0.01). EC-HO-1 increased angiopoietin-1 (ANG-1), vascular endothelial growth factor A (VEGF), and platelet derived growth factor (PDGF)-AA,−BB (p<0.05). The addition of ANG-1 to adipogenic media resulted in the inhibition of adipogenesis (8.1 ± 0.1, p<0.01). Conclusion: Targeting HO-1 to ECs resulted in the attenuation of blood pressure and the prevention of body weight gain resulting in increased ANG-1, PDGF, and VGEF levels and the reprogramming of MSCs derived adipocytes to produce healthy and smaller adipocytes with the release of adiponectin.


Author(s):  
Pare DRAMANE ◽  
Hilou ADAMA ◽  
Adrian POTÂRNICHE ◽  
Mabozou KPEMISSI ◽  
Orsolya SÁRPATAKI ◽  
...  

Caralluma acutangula (Decne.) (CA) (Asclepiadaceae) is a medicinal plant traditionally used in Burkina Faso for the management of weight. The aim of this study was to evaluate the effect of extract of CA on body weight, food intake, blood biochemistry parameters on experimental obesity rat model. One group received CA 400 mg/kg b.w. per day and was fed on hyperlipidic diet (HD), while the control group received HD only for three weeks long. The phytochemical investigation of extract showed a high total phenolic content (36.21±1.36 mg GAE/100mg of extract) and total flavonoids (4.98 ±0.31 QE/100 mg of extract). In the end, CA-HD treated group had a body weight loss of 2%, compared to HD group who presented a body weight gain of 15%. The CA-HD treated group showed also a lower levels of plasma triglyceride (136.57±13.82 mg/dL) and glycemia (187.74±31.16 mg/dL) compared to HD (206.02±23.82 and respectively 230.96±79.07 mg/dL) (p<0.05). CA extract also showed a good anti-oxidant activity in vivo (effect on antioxydant enzyme (MDA, GPX, SOD) and in vitro (inhibition of DPPH radical, ferric ion reduction). This study showed that CA is a potential natural remedy for the control of body weight and alleviation of obesity related disease.


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