scholarly journals 3,5-Diiodo-L-Thyronine (T2) Administration Affects Visceral Adipose Tissue Inflammatory State in Rats Receiving Long-Lasting High-Fat Diet

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Petito ◽  
Federica Cioffi ◽  
Elena Silvestri ◽  
Rita De Matteis ◽  
Davide Lattanzi ◽  
...  

3,5-diiodo-thyronine (T2), an endogenous metabolite of thyroid hormones, exerts beneficial metabolic effects. When administered to overweight rats receiving a high fat diet (HFD), it significantly reduces body fat accumulation, which is a risk factor for the development of an inflammatory state and of related metabolic diseases. In the present study, we focused our attention on T2 actions aimed at improving the adverse effects of long-lasting HFD such as the adipocyte inflammatory response. For this purpose, three groups of rats were used throughout: i) receiving a standard diet for 14 weeks; ii) receiving a HFD for 14 weeks, and iii) receiving a HFD for 14 weeks with a simultaneous daily injection of T2 for the last 4 weeks. The results showed that T2 administration ameliorated the expression profiles of pro- and anti-inflammatory cytokines, reduced macrophage infiltration in white adipose tissue, influenced their polarization and reduced lymphocytes recruitment. Moreover, T2 improved the expression of hypoxia markers, all altered in HFD rats, and reduced angiogenesis by decreasing the pro-angiogenic miR126 expression. Additionally, T2 reduced the oxidative damage of DNA, known to be associated to the inflammatory status. This study demonstrates that T2 is able to counteract some adverse effects caused by a long-lasting HFD and to produce beneficial effects on inflammation. Irisin and SIRT1 pathway may represent a mechanism underlying the above described effects.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maki Murakoshi ◽  
Tomohito Gohda ◽  
Eri Adachi ◽  
Saki Ichikawa ◽  
Shinji Hagiwara ◽  
...  

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.


2018 ◽  
Vol 239 (2) ◽  
pp. 229-240 ◽  
Author(s):  
A Feraco ◽  
A Armani ◽  
R Urbanet ◽  
A Nguyen Dinh Cat ◽  
V Marzolla ◽  
...  

Obesity is a major risk factor that contributes to the development of cardiovascular disease and type 2 diabetes. Mineralocorticoid receptor (MR) expression is increased in the adipose tissue of obese patients and several studies provide evidence that MR pharmacological antagonism improves glucose metabolism in genetic and diet-induced mouse models of obesity. In order to investigate whether the lack of adipocyte MR is sufficient to explain these beneficial metabolic effects, we generated a mouse model with inducible adipocyte-specific deletion of Nr3c2 gene encoding MR (adipo-MRKO). We observed a significant, yet not complete, reduction of Nr3c2 transcript and MR protein expression in subcutaneous and visceral adipose depots of adipo-MRKO mice. Notably, only mature adipocyte fraction lacks MR, whereas the stromal vascular fraction maintains normal MR expression in our mouse model. Adipo-MRKO mice fed a 45% high-fat diet for 14 weeks did not show any significant difference in body weight and fat mass compared to control littermates. Glucose and insulin tolerance tests revealed that mature adipocyte MR deficiency did not improve insulin sensitivity in response to a metabolic homeostatic challenge. Accordingly, no significant changes were observed in gene expression profile of adipogenic and inflammatory markers in adipose tissue of adipo-MRKO mice. Moreover, pharmacological MR antagonism in mature primary murine adipocytes, which differentiated ex vivo from WT mice, did not display any effect on adipokine expression. Taken together, these data demonstrate that the depletion of MR in mature adipocytes displays a minor role in diet-induced obesity and metabolic dysfunctions.


2017 ◽  
Vol 42 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Natalia de las Heras ◽  
María Valero-Muñoz ◽  
Beatriz Martín-Fernández ◽  
Sandra Ballesteros ◽  
Antonio López-Farré ◽  
...  

Hypolipidemic and hypoglycemic properties of ginger in animal models have been reported. However, information related to the mechanisms and factors involved in the metabolic effects of ginger at a hepatic level are limited. The aim of the present study was to investigate molecular factors involved in the hypoglycemic and hypolipidemic effects of a hydroethanolic ginger extract (GE) in the liver of rats fed a high-fat diet (HFD). The study was conducted in male Wistar rats divided into the following 3 groups: (i) Rats fed a standard diet (3.5% fat), the control group; (ii) rats fed an HFD (33.5% fat); and (iii) rats fed an HFD treated with GE (250 mg·kg−1·day−1) for 5 weeks (HFD+GE). Plasma levels of glucose, insulin, lipid profile, leptin, and adiponectin were measured. Liver expression of glycerol phosphate acyltransferase (GPAT), cholesterol 7 alpha-hydroxylase, peroxisome proliferator-activated receptors (PPAR), PPARα and PPARγ, glucose transporter 2 (GLUT-2), liver X receptor, sterol regulatory element-binding protein (SREBP1c), connective tissue growth factor (CTGF), and collagen I was measured. Data were analyzed using a 1-way ANOVA, followed by a Newman−Keuls test if differences were noted. The study showed that GE improved lipid profile and attenuated the increase of plasma levels of glucose, insulin, and leptin in HFD rats. This effect was associated with a higher liver expression of PPARα, PPARγ, and GLUT-2 and an enhancement of plasma adiponectin levels. Furthermore, GE reduced liver expression of GPAT, SREBP1c, CTGF, and collagen I. The results suggest that GE might be considered as an alternative therapeutic strategy in the management of overweight and hepatic and metabolic−related alterations.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 436-436
Author(s):  
Hercia Martino ◽  
Mariana Grancieri ◽  
Renata Toledo ◽  
Thaisa Veridiano ◽  
Cintia Tomaz Sant'Ana ◽  
...  

Abstract Objectives To evaluate the effects of digested total proteins (DTP) from chia seed to prevent adipogenesis and adipose tissue inflammation in mice fed a high-fat diet. Methods C57Bl/6 black mice (n = 44; 8 weeks old) where divided in 4 groups (n = 12 each): negative control (NC; standard diet AIN-93M); positive control (PC; high fat diet- HFD- 60% of lipids); normal diet + DTP (NH; standard diet + 400 mg/kg of body/day of DTP); high-fat diet plus DTP (HFH; HFD + 400 mg/kg of body/day of DTP). After 9 weeks of treatment, the animals were euthanized and the blood and the adipose tissue (total) were collected. Plasma was used to analyze total cholesterol, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, triacylglycerides (TGL), aspartate (AST) and alanine (ALT) aminotransferase levels by colorimetry. Waist circumference was measured by metric tape in the middle portion between the anus and mouth and the quantity of p-p65-NF-κB and PPAR-Y ELISA test. Histomorphometric analysis was determined in adipose tissue staining with hematoxylin/eosin to determined adipocytes area and foci of inflammation by the average of 1000 cells/group. Data were analyzed by ANOVA and post-hoc of Newman-Kews (P < 0.05). The study protocol was approved by the Ethics Committee of the Federal University of Viçosa (Protocol 01/2019). Results DTP from chia seed reduced the plasmatic levels of total cholesterol (−17.5%), LDL (−42.8%), TGL (−12.3%), and waist circumference (−5.5%) in obesity mice DTP-treated (P < 0.05). The treatment with DTP reduced the adipocytes area in HFH group by −15.1% and the foci of inflammation in −78.1% in comparison with PC (P < 0.05). The levels of p-p65-NF-κB in adipose tissue were reduced by DTP in mice fed a HFD in −41.1% (P < 0.05). However, PPAR-γ levels, body fat (%), Lee index, and HDL levels were not changed by DTP (P > 0.05). The levels of AST and ALT were not affected by HFD or DTP (P > 0.05). Conclusions DTP from chia seed had an anti-inflammatory and even an anti-adipogenic effect. These results show the effectiveness of digested proteins from chia seed against obesity and its associated inflammation. Funding Sources CNPq and CAPES (Brazil), and ACES (USA).


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Eva Gatineau ◽  
Dianne Cohn ◽  
Ming Gong ◽  
Frédérique Yiannikouris

Obesity contributes to approximatively 2.5 million deaths every year and is associated with life threatening conditions including hypertension. Recently, we found that constitutive deletion of adipocyte (pro)renin-receptor (PRR) prevented high-fat diet-induced obesity through a drastic decrease in fat mass. However, adipocyte PRR deficient mice were characterized by a fatty liver and by an elevated systolic blood pressure (SBP), classic features of models of lipodystrophy. The purpose of this study was to investigate whether the temporally-controlled deletion of adipocyte PRR in obese mice reverses obesity related hypertension. After 18 weeks of high fat diet, inducible adipocyte-PRR deficient ( PRR ERT ) and control ( PRR fl/Y ) male mice (n=7-11 mice/ group) were injected intraperitoneally with tamoxifen (TMX) for 5 consecutive days. Body weight, body composition and blood pressure, measured by radiotelemetry in a subgroup of mice (n=2-4 mice/ group), were recorded before and after TMX injection. The inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly body weights ( PRR fl/fl , 46.6 ± 1.3 g; PRR ERT , 42.1 ± 1.4 g, P<0.05) and fat mass ( PRR fl/fl , 15.8 ± 1.0 g; PRR ERT , 8.1 ± 0.7 g, P<0.05) compared to control mice. PPARγ, FABP4 and FAS mRNA levels were significantly decreased by 68% (6.8 out 10), 80% (8 out 10) and 68% (6.8 out 10) respectively in white adipose tissues of PRR ERT mice suggesting that PRR positively regulated adipogenesis and lipid metabolism in adipose tissue. In addition, the inducible deletion of adipocyte PRR in PRR ERT mice decreased significantly SBP compared to control mice ( PRR fl/fl , -4.3 ± 3.2 g; PRR ERT , -10.2 ± 2.4 g, P<0.05). Interestingly, adipocyte angiotensinogen mRNA abundance was significantly decreased in adipose tissue of PRR ERT mice fed a standard diet suggesting that the decrease in blood pressure might be mediated by a local renin angiotensin system (RAS). The measurement of local (liver, kidney, adipose tissue and brain) and systemic RAS in HF-fed mice is under investigation. Taken together, our results highlight a new signaling pathway in which PRR regulates adipogenesis, lipid metabolism and blood pressure. PRR could represent a new potential therapeutic target for obesity and hypertension.


Author(s):  
Carolina M. Saullo ◽  
Yuri K. Sinzato ◽  
Verônyca G. Paula ◽  
Franciane Q. Gallego ◽  
José E. Corrente ◽  
...  

Abstract Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.


2013 ◽  
Vol 304 (10) ◽  
pp. E1053-E1063 ◽  
Author(s):  
Johanna L. Barclay ◽  
Anton Shostak ◽  
Alexei Leliavski ◽  
Anthony H. Tsang ◽  
Olaf Jöhren ◽  
...  

Perturbation of circadian rhythmicity in mammals, either by environmental influences such as shiftwork or by genetic manipulation, has been associated with metabolic disturbance and the development of obesity and diabetes. Circadian clocks are based on transcriptional/translational feedback loops, comprising positive and negative components. Whereas the metabolic effects of deletion of the positive arm of the clock gene machinery, as in Clock- or Bmal1-deficient mice, have been well characterized, inactivation of Period genes ( Per1–3) as components of the negative arm have more complex, sometimes contradictory effects on energy homeostasis. The CRYPTOCHROMEs are critical interaction partners of PERs, and simultaneous deletion of Cry1 and - 2 results in behavioral and molecular circadian arrhythmicity. We show that, when challenged with a high-fat diet, Cry1/2−/− mice rapidly gain weight and surpass that of wild-type mice, despite displaying hypophagia. Transcript analysis of white adipose tissue reveals upregulated expression of lipogenic genes, many of which are insulin targets. High-fat diet-induced hyperinsulinemia, as a result of potentiated insulin secretion, coupled with selective insulin sensitivity in adipose tissue of Cry1/2−/− mice, correlates with increased lipid uptake. Collectively, these data indicate that Cry deficiency results in an increased vulnerability to high-fat diet-induced obesity that might be mediated by increased insulin secretion and lipid storage in adipose tissues.


2014 ◽  
Vol 112 (4) ◽  
pp. 520-535 ◽  
Author(s):  
Bérengère Benoit ◽  
Pascale Plaisancié ◽  
Alain Géloën ◽  
Monique Estienne ◽  
Cyrille Debard ◽  
...  

Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.


Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4238-4245 ◽  
Author(s):  
Julieta Díaz-Delfín ◽  
Elayne Hondares ◽  
Roser Iglesias ◽  
Marta Giralt ◽  
Carme Caelles ◽  
...  

Fibroblast growth factor 21 (FGF21) is a member of the FGF family that reduces glycemia and ameliorates insulin resistance. Adipose tissue is a main target of FGF21 action. Obesity is associated with a chronic proinflammatory state. Here, we analyzed the role of proinflammatory signals in the FGF21 pathway in adipocytes, evaluating the effects of TNF-α on β-Klotho and FGF receptor-1 expression and FGF21 action in adipocytes. We also determined the effects of rosiglitazone on β-Klotho and FGF receptor-1 expression in models of proinflammatory signal induction in vitro and in vivo (high-fat diet-induced obesity). Because c-Jun NH2-terminal kinase 1 (JNK1) serves as a sensing juncture for inflammatory status, we also evaluated the involvement of JNK1 in the FGF21 pathway. TNF-α repressed β-Klotho expression and impaired FGF21 action in adipocytes. Rosiglitazone prevented the reduction in β-Klotho expression elicited by TNF-α. Moreover, β-Klotho levels were reduced in adipose tissue from high-fat diet-induced obese mice, whereas rosiglitazone restored β-Klotho to near-normal levels. β-Klotho expression was increased in white fat from JNK1−/− mice. The absence of JNK1 increased the responsiveness of mouse embryonic fibroblast-derived adipocytes and brown adipocytes to FGF21. In conclusion, we show that proinflammatory signaling impairs β-Klotho expression and FGF21 responsiveness in adipocytes. We also show that JNK1 activity is involved in modulating FGF21 effects in adipocytes. The impairment in the FGF21 response machinery in adipocytes and the reduction in FGF21 action in response to proinflammatory signals may play important roles in metabolic alterations in obesity and other diseases associated with enhanced inflammation.


2020 ◽  
Vol 129 (4) ◽  
pp. 909-919
Author(s):  
Alexander T. Sougiannis ◽  
Brandon N. VanderVeen ◽  
Taryn L. Cranford ◽  
Reilly T. Enos ◽  
Kandy T. Velazquez ◽  
...  

We examined the immune and inflammatory status of adipose tissue in mice after they underwent weight loss followed by partial weight regain. We show an increase in selected immune cells and inflammatory mediators, in high-fat diet-fed mice that had prior exposure to a high-fat diet. Although weight fluctuations appear to exacerbate immune cell abundance and inflammation in adipose tissue, severity is less than in mice that were exposed to sustained high-fat diet feedings.


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