Rat Adipose Research Articles

Modulation of lipid transport and accumulation in the placenta from overweight rats by butyrate

Modulation of lipid transport and accumulation in the placenta from overweight rats by butyrate

Obesogenic effects of the contaminant 3MC are more pronounced in the female offspring from overweight rats than in control offspring

Obesogenic effects of the contaminant 3MC are more pronounced in the female offspring from overweight rats than in control offspring

RETRACTION: Pioglitazone Improves Lipid and Insulin Levels in Overweight Rats on a High Cholesterol and Fructose Diet by Decreasing Hepatic Inflammation.

RETRACTION: Pioglitazone Improves Lipid and Insulin Levels in Overweight Rats on a High Cholesterol and Fructose Diet by Decreasing Hepatic Inflammation.

Metformin treatment prevents experimental metabolic syndrome-induced femoral bone marrow adiposity in rats.

Motivation for the study. Most research supports a negative association between metabolic syndrome and bone health, although there is an overall lack of consensus. Therefore, there is a need for research in this area to develop a better understanding. Main findings. Metabolic syndrome induced by a fructose-rich diet increases the adipogenic predisposition of bone marrow progenitor cells and femoral medullary adiposity in rats. Furthermore, this can be partially prevented by co-treatment with metformin. Implications. Experimental metabolic syndrome has negative effects on bone tissue and can be prevented by oral treatment with metformin as a normoglycemic drug. To determine the effect of metformin (MET) treatment on adipogenic predisposition of bone marrow progenitor cells (BMPC), bone marrow adiposity and bone biomechanical properties. 20 young adult male Wistar rats were sorted into four groups. Each of the groups received the following in drinking water: 100% water (C); 20% fructose (F); metformin 100 mg/kg wt/day (M); or fructose plus metformin (FM). After five weeks the animals were sacrificed. Both humeri were dissected to obtain BMPC, and both femurs were dissected to evaluate medullary adiposity (histomorphometry) and biomechanical properties (3-point bending). BMPC were cultured in vitro in adipogenic medium to evaluate RUNX2, PPAR-γ and RAGE expression by RT-PCR, lipase activity and triglyceride accumulation. The fructose-rich diet (group F) caused an increase in both triglycerides in vitro, and medullary adiposity in vivo; being partially or totally prevented by co-treatment with metformin (group FM). No differences were found in femoral biomechanical tests in vivo, nor in lipase activity and RUNX2/PPAR-γ ratio in vitro. DRF increased RAGE expression in BMPC, being prevented by co-treatment with MET. Metabolic syndrome induced by a fructose-rich diet increases femoral medullary adiposity and, in part, the adipogenic predisposition of BMPC. In turn, this can be totally or partially prevented by oral co-treatment with MET.

Intestinal alterations and mild glucose homeostasis impairments in the offspring born to overweight rats

The gut plays a crucial role in metabolism by regulating the passage of nutrients, water and microbial-derived substances to the portal circulation. Additionally, it produces incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1, encoded by gcg gene) in response to nutrient uptake. We aimed to investigate whether offspring from overweight rats develop anomalies in the barrier function and incretin transcription. We observed pro-inflammatory related changes along with a reduction in Claudin-3 levels resulting in increased gut-permeability in fetuses and offspring from overweight rats. Importantly, we found decreased gip mRNA levels in both fetuses and offspring from overweight rats. Differently, gcg mRNA levels were upregulated in fetuses, downregulated in female offspring and unchanged in male offspring from overweight rats. When cultured with high glucose, intestinal explants showed an increase in gip and gcg mRNA levels in control offspring. In contrast, offspring from overweight rats did not exhibit any response in gip mRNA levels. Additionally, while females showed no response, male offspring from overweight rats did exhibit an upregulation in gcg mRNA levels. Furthermore, female and male offspring from overweight rats showed sex-dependent anomalies when orally challenged with a glucose overload, returning to baseline glucose levels after 120 min.These results open new research questions about the role of the adverse maternal metabolic condition in the programming of impairments in glucose homeostasis, enteroendocrine function and gut barrier function in the offspring from overweight mothers and highlight the importance of a perinatal maternal healthy metabolism.

Uxi (Endopleura uchi (Huber) Cuatrec) bark extract mitigates HFD-induced adiposity in rats via targeting oxidative stress, and lipogenic genes expression

Here, we compared the modulatory effects of different dose levels of Uxi (Endopleura uchi aqueous bark extract, EUAE) vs simvastatin (SIM) on hyperlipidemia, metabolic stress, and liver dysfunction in HFD-induced obese rats. HFD significantly increased BMI, lee index, body adipose index, atherogenic indices, cellular toxicity markers, blood glucose level, adipokines, pro-inflammatory mediators, lipid peroxidation and promoted lipid accumulation and HMGCR and ACC. Furthermore, it significantly decreased antioxidants, ghrelin, and AG/UAG ratio as well as hepatic glycogen content, while these changes were mitigated by either SIM or EUAE treatment. The expression of FASN & SREBP1c genes were elevated in the HFD group, with downregulation of PPARα expression. These alterations were ameliorated by SIM or EUAE treatment. The beneficial effects of EUAE may be attributed to its phenolic compounds and their derivatives. This study supports the hypothesis that Uxi may have antihyperlipidemic, antioxidant, hepatoprotective, and anti-inflammatory properties in rat model of obesity.

Burn wound healing using adipose-derived mesenchymal stem cells and manganese nanoparticles in polycaprolactone/gelatin electrospun nanofibers in rats.

Wound healing is a major therapeutic concern in regenerative medicine. The current study aimed to investigate the second-degree burn wound treatment in rats using rat adipose- derived stem cells (ADSCs) and manganese nanoparticles (MnO2-NPs) in a polycaprolactone/gelatin electrospun nanofiber scaffold. After the synthesis of nanoparticles and electrospinning of nanofibers, the SEM analysis, contact angle, mechanical strength, blood compatibility, porosity, swelling, biodegradability, cell viability, and adhesion assays were performed. According to the results, the PCL/Gel/5%MnO2-NPs nanofiber (Mn-5%) was determined to be the most suitable scaffold. The ADSCs-seeded Mn-5% scaffolds were applied as a burn wound dressing. The wound closure rate, IL-1β, and IL-6 level, hydroxyproline, and glycosaminoglycans content were measured, and the hematoxylin and eosin, Masson's trichrome, and immunohistochemistry stainings were carried out. Based on the results, in Mn+S (ADSCs+PCL/Gel/5%MnO2-NPs nanofiber) and N+S (ADSCs+PCL/Gel nanofiber) groups, the IL-6 and IL-1β levels were reduced, and the percentage of wound closure, glycosaminoglycans, and hydroxyproline content were increased compared to the control group (P<0.05). Also, the lowest amount of α-SMA was observed in these two groups, demonstrating stem cells' role in reducing α-SMA levels and thus preventing fibrosis. Moreover, the amount of α-SMA in the Mn+S group is lower than in the N+S group and, is closer to healthy skin. According to histology results, the best type of treatment was observed in the Mn+S group. In conclusion, the ADSCs-seeded PCL/Gel/5%MnO2-NPs scaffold demonstrated considerable therapeutic effects in burn wound healing.

Oral curcumin phytosome supplementation improves anthropometric measures of adiposity and enhances endothelial function in rats on a high-fat-diet regimen

Objectives: Curcumin has a protective role in endothelial function and nitric oxide (NO) production in animal models of different diseases; however, the role of curcumin on aortic reactivity in rats placed on a high-fat diet (HFD) remains unclear. This study aims to determine whether oral curcumin phytosome supplementation can reduce adiposity and enhance endothelial function. Materials and Methods: Rats were assigned to one of three groups: normal diet (ND), HFD for 20 weeks, and HFD supplemented with curcumin phytosome (HFD + Curcumin). Anthropometric measures were recorded weekly for the three groups, until the end of the feeding regimen. After 20 weeks of feeding on HFD, myographic investigations were conducted on thoracic aortic rings dissected from HFD and HFD + Curcumin rats. The response to high potassium chloride (KCl), incremental doses of phenylephrine (Phe) before and after L-NAME treatment, acetylcholine (ACh), or sodium nitroprusside (SNP), was evaluated. ACh-induced relaxation was also assessed in HFD + Curcumin rats, after preincubation with chromium III-mesoporhyrin. Results: HFD rats exhibited increased adiposity measures, some of which were negatively correlated with vasorelaxation response to ACh. HFD + Curcumin rats had reduced anthropometric measures, compared to HFD rats. Aortic rings from HFD and HFD + Curcumin rats exhibited comparable contractile responses to KCl and Phe. The difference in contractile response to Phe before and after L-NAME incubation was greater for HFD + Curcumin rats. ACh induced greater vasorelaxant responses in HFD + Curcumin rats. There was no group difference in the relaxant response to SNP. In HD + Curcumin rats, chromium III mesoporphyrin significantly reduced ACh-induced relaxations. Conclusion: Oral curcumin phytosome supplementation could reduce adiposity in rats placed on an HFD and may have enhanced basal and stimulated NO release from the endothelium, and heme oxygenase-1 may partly mediate this curcumin protective role. This study provides evidence that this curcumin formulation, taken as a daily supplement, may be effective in providing some protection against adiposity-associated adverse cardiovascular disorders.

The ketogenic diet promotes triacylglycerol recycling in white adipose tissue and uncoupled fat oxidation in brown adipose tissue, but does not reduce adiposity in rats

The purpose of this study was to determine whether the weight-reducing and fat burning effects of the ketogenic diet (KD) could be attributed to alterations in the energy dissipating pathways of brown adipose tissue (BAT) uncoupled oxidation, and white adipose tissue (WAT) browning and triacylglycerol (TAG) recycling. To investigate this, male Wistar rats were fed one of the following three diets for either 8 or 16 weeks: a standard chow (SC), a high-fat, sucrose-enriched (HFS) obesogenic diet, or a KD. At the end of the intervention, subcutaneous inguinal (Sc Ing) and epididymal (Epid) fat, and interscapular and aortic BAT (iBAT and aBAT, respectively) were extracted. These tissues were used for the analysis of proteins involved in WAT browning and thermogenesis. Isolated adipocytes from WAT were assayed for basal and isoproterenol (Iso)-stimulated lipolysis and basal and insulin-stimulated lipogenesis, and BAT adipocytes were assayed for the determination of coupled and uncoupled glucose and palmitate oxidation. Adiposity similarly increased in HFS- and KD-fed rats at weeks 8 and 16. However, in HFS-fed animals insulin-stimulated lipogenesis and Iso-stimulated lipolysis were impaired in WAT adipocytes, whereas in KD-fed animals these pathways remained intact. The KD also significantly elevated WAT glycerol kinase levels, and favored TAG recycling under conditions of enhanced lipolysis. In BAT, the KD significantly increased uncoupling protein-1 levels and uncoupled fat oxidation. In summary, the KD preserved insulin sensitivity and lipolytic capacity in WAT and also upregulated energy-dissipating pathways in BAT, but it was not sufficient to prevent an increase in adiposity.

Improvement of metabolic and histological changes of adiposity in rats by synthetic oleoyl chalcones.

We previously reported that synthetic oleoyl chalcones had favorable effect to alleviate metabolic consequences of obesity in male SD rats. In this work, we prepared and characterized by spectroscopic tools, a set of six oleoyl chalcones ( 5 a-c , 10 and 11 a , b ). The comparative effects of the previously prepared oleoyl chalcones and their new synthetic analogs on metabolic and histological changes in obese male SD rats were studied. It was found that the oleoyl chalcones III a and IV were still the best in improving many metabolic parameters e.g. FBG, FI, ISI, TG, and total cholesterol. They cured systemic inflammation, through inhibition of the TNF-α and induction of adiponectin production. Moreover, chalcones III a and IV alleviated the oxidative stress accompanying obesity through induction of the antioxidant enzymes GPX, SOD and CAT besides, GSH. Interestingly, chalcones III a and IV exerted hepatoprotective potency and ameliorated the manifestations of NAFLD via inhibition of apoptosis and induction of autophagy of hepatic cells. In conclusion, the oleoyl chalcones III a and IV were the most effective candidates among the series of synthetic chalcones in correcting body weight and the consequent metabolic and histological changes in adiposity.

Transplantation of adipose-derived mesenchymal stem cells ameliorates acute hepatic injury caused by nonsteroidal anti-inflammatory drug diclofenac sodium in female rats

BackgroundAlthough the beneficial role of adipose-derived mesenchymal stem cells (AD-MSCs) in acute liver injury has been addressed by numerous studies employing different liver injury inducers, the role of rat AD-MSCs (rAD-MSCs) in diclofenac sodium (DIC) – induced acute liver injury has not yet been clarified. ObjectiveThis study aimed to investigate whether rat adipose- rAD-MSCs injected intraperitoneal could restore the DIC-induced hepatoxicity. MethodsHepatotoxicity was induced by DIC in a dose-based manner, after which intraperitoneal injection of rAD-MSCs was performed. ResultsHere, the transplanted cells migrated to the injured liver, and this was evidenced by detecting the specific SRY in the liver samples. After administering DIC, a significant decrease in body weight, survival rate, serum proteins, antioxidants, anti-apoptotic gene expression, and certain growth factors, whereas hepatic-specific markers, pro-inflammatory mediators, and oxidative, pro-apoptotic, and ER-stress markers were elevated. These adverse effects were significantly recovered after engraftment with rAD-MSCs. This was evidenced by enhanced survival and body weight, improved globulin and albumin values, increased expression of SOD, GPx, BCL-2, VEGF, and FGF-basic expression, and decreased serum ALT, AST, ALP, and total bilirubin. rAD-MSCs also reduced liver cell damage by suppressing the expression of MDA, IL-1B, IL-6, BAX, JNK, GRP78/BiP, CHOP, XBP-1, and cleaved caspase 3/7. Degenerative hepatic changes and multifocal areas of fatty change within liver cells were observed in DIC-received groups. These changes were improved with the transplantation of rAD-MSCs. ConclusionsWe could conclude that targeted AD-MSCs could be applied to reduce hepatic toxicity caused by NSAIDs (DIC).

Effect of Pomegranate Peel on Body Weight, Blood Sugar and Lipid Levels of Overweight Rats

Effect of Pomegranate Peel on Body Weight, Blood Sugar and Lipid Levels of Overweight Rats

Effects of Dapagliflozin on Adipose and Liver Fatty Acid Composition and mRNA Expression Involved in Lipid Metabolism in High-Fat-Fed Rats.

SGLT2 inhibitor enhances not only glucose excretion but also fatty acid utilization. Those facts suggest that SGLT2 inhibitor affects fat accumulation and lipid storage. In the present study, we evaluated the effects of dapagliflozin on fatty acid composition and gene expression involved in fatty acid metabolism in rat adipose and liver tissues. We administered 1 mg/kg/day dapagliflozin for 7 weeks to male high-fat-fed rats (DAPA group), and then weights and 22 fatty acid contents in the epididymal (EPI), mesenteric (MES), retroperitoneal (RET), and subcutaneous (SUB) adipose tissues, and the liver were compared with the vehicle-administered control group. In the EPI, RET, and SUB in the DAPA group, contents of several fatty acids were lower (P<0.05) than those in the control group, while no significant difference was detected in tissue weight. In the MES, tissue weight and a wide variety of fatty acid contents, including saturated, monounsaturated, and polyunsaturated fatty acids, were lower (P<0.05). As for the liver tissue, no significant difference was observed in fatty acid contents between the groups. mRNA expression of Srebp1c in EPI was significantly higher (P<0.05) in the DAPA group than in the control group, while Scd1 expression in the liver was lower (P<0.01). These results suggest that dapagliflozin might suppress lipid accumulation especially in the MES, and could reduce contents of fatty acids not in the liver but in adipose tissues in high-fat-fed rats. In addition, dapagliflozin could influence mRNA expression involved in lipogenesis in the EPI and liver.

Liver steatosis, cardiac and renal fibrosis, and hypertension in overweight rats: Angiotensin-(3–4)-sensitive hepatocardiorenal syndrome

Overweight/obesity is a growing pandemic that affects many organs and tissues. We have investigated whether a high-lipid diet provokes an imbalance between type 1 and type 2 angiotensin II (Ang II) receptors signaling, leading to liver alterations associated with cardiovascular and kidney disturbances. Chronic administration of a high-lipid diet can provoke hepatocardiorenal syndrome resulting from activation of the Ang II→type 1 receptor axis, which is entirely counteracted by Ang-(3–4), the allosteric enhancer of the Ang II→type 2 receptor pathway.

Comparison of Antioxidant Effect of Crocus Sativus and Vitamin E on Amakicin Induced Nephrotoxicity in Albino Rats

ABSTRACT&#x0D; Objectives: The present study evaluated the protective effect of Crocus Sativus against Amikacin-induced Nephrotoxicity.&#x0D; Methods: The prospective descriptive study was conducted at the department of orthopedic surgery, Dr. Ruth KM Pfau Adult laboratory albino rats of the Wistar strain were used in this experimental study. In this study, 75 albino rats were subdivided into 3 groups, including experimental groups B and C. The control group (A) received normal saline intraperitoneally, group (B) received Amikacin 30mg/kg body weight intraperitoneally and Group (C) received Crocus sativus 50 mg/kg body weight orally and vitamin E orally in a dose of 50mg/kg of body weight. Kidneys of rats obtained after dissection were processed, sectioned, and stained in PAS Hematoxylin and Gomoris Methenamine Silver stains. The present study was conducted at Dow University of Health Sciences in the Institute of Biomedical Sciences and Animal House of Dow University and Dow Diagnostic Research and Reference Laboratory. The duration of the study was Three months. Inclusion criteria were Albino rats of both sexes, kidneys of either side (right &amp; left), rats with an approximate weight of 140 to 180 grams were included in the study. Exclusion criteria were overweight rats and pregnant rats.&#x0D; Results: A significant increase in kidney weight was observed in group B. A considerable addition was observed in proximal tubular in groups B and C. A considerable increase was also observed in the number of intact proximal tubule nuclei and the nuclear diameter of groups B &amp; C.&#x0D; Conclusion: The study provides evidence that Crocus Sativus has protective effects in Amikacin-induced nephrotoxicity, comparable to widely used Antioxidant Vitamin E. The study recommends the addition of Crocus Sativus in dietary supplements after further evaluation in human subjects.

Influence of a diet rich in linoleic acid on mRNA levels for enzymes of branched chain amino acids metabolism in rat's adipose tissue: a pilot study.

White adipose tissue plays an important role in the catabolism of branched chain amino acids (BCAAs). Two initial regulatory steps in BCAAs catabolism are catalyzed by branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase complex (BCKDH complex), respectively. It has been demonstrated that synthetic ligands for PPARγ receptors increased mRNA levels for enzymes involved in BCAAs catabolism. We hypothesized that feeding rats with diet rich in linoleic acid (LA), a natural PPARγ agonist modifies mRNA levels for enzymes catalyzing BCAAs degradation in adipose tissue. The current pilot study was aimed at the investigation of the effect of diet rich in LA on mRNA levels for BCATm, branched chain α-keto acid dehydrogenase (E1 component of the BCKDH), and mRNA levels for the regulatory enzymes of BCKDH complex, a specific kinase (BDK) and a specific phosphatase (PPM1K) in epididymal white adipose tissue (eWAT). Wistar male rats were fed with high unsaturated fat diet containing mainly linoleic acid (study group) or with the high saturated fat diet (control group). The relative mRNA levels were quantified by reverse transcription-PCR. We have found that in rats fed diet rich in LA mRNA level for BCATm decreased, while mRNA amount for BDK increased. There was no difference between mRNA levels for BCKDH E1 and PPM1K. It is conceivable that changes in mRNA levels for enzymes involved in BCAAs metabolism in eWAT may lead to modification of BCAAs catabolic rate. Further studies are required to fully elucidate this issue.

Differential analysis of chromatin accessibility and gene expression profiles identifies cis-regulatory elements in rat adipose and muscle

Chromatin accessibility is a key factor influencing gene expression. We optimized the Omni-ATAC-seq protocol and used it together with RNA-seq to investigate cis-regulatory elements in rat white adipose and skeletal muscle, two tissues with contrasting metabolic functions. While promoter accessibility correlated with RNA expression, integration of the two datasets identified tissue-specific differentially accessible regions (DARs) that predominantly localized in intergenic and intron regions. DARs were mapped to differentially expressed (DE) genes enriched in distinct biological processes in each tissue. Randomly selected DE genes were validated by qPCR. Top enriched motifs in DARs predicted binding sites for transcription factors (TFs) showing tissue-specific up-regulation. The correlation between differential chromatin accessibility at a given TF binding motif and differential expression of target genes further supported the functional relevance of that motif. Our study identified cis-regulatory regions that likely play a major role in the regulation of tissue-specific gene expression in adipose and muscle.

Abstract 60: Perirenal Adipose Hypertrophy In A Congenic LH Rat: A Role For C17h6orf52

Central obesity, high blood pressure, dyslipidemia, and insulin resistance are a collection of cardiovascular and metabolic risk factors that form the basis of the Metabolic Syndrome (MetS) and represent a major public health burden worldwide. The phenotypes that define MetS are all highly heritable, but their genetic complexity necessitates the use of animal models to tease apart novel pathways. The Lyon Hypertensive (LH) rat is a well-characterized model of MetS, exhibiting profound differences in features of MetS compared to its metabolically healthy control, the Lyon Normotensive (LN) rat. To understand the genomic causes of MetS, we developed a congenic rat model, where a portion of LN chromosome 17 is introgressed on the LH genomic background. Male and female LH congenic (CON) rats and LH controls were phenotyped for a variety of MetS characteristics, including body growth and composition by nuclear magnetic resonance (NMR), metabolic rate (Promethion system), and adipose tissue collection and histological examination. There were significant decreases in body weight in the CON rats of both sexes compared to LH. We also found significant female-specific increases in body fat and decreases in metabolic rate. Tissue collection revealed the source of the increased adiposity in the female CON rats was specific to perirenal white adipose tissue (PWAT) and was further explained by significant hypertrophy in those adipocytes. Genome resequencing of the parental strains identified a gene, C17h6orf52 , as a strong contender underlying the phenotype differences in the congenics, with predicted amino acid changes and the loss of Nr2f2 transcription factor binding sites.

Abstract P177: Sex- And Strain- Specific Metabolic Effects Of Postnatal Bpf Exposure In Heterogeneous Stock Rat Founding Inbred Strains

Bisphenol F (BPF) is increasing substituting bisphenol A (BPA), an endocrine disruptor associated with cardiometabolic disease, in manufacturing polycarbonates and consumer products. Interindividual variation in bisphenol levels suggests that gene x environment (GxE) interactions influence cardiometabolic disease risk from bisphenol exposure. Studies show that BPF is a potent endocrine disruptor with effects on thyroid, reproductive health, and neuroendocrine functions. Traditional in vivo toxicity studies are performed in isogenic or genetically undefined outbred rodents, leading to conflicting results possibly due to GxE interactions. The N/NIH Heterogeneous Stock (HS) rats are a genetically heterogeneous population amenable to genetic study. Our overall study hypothesis is that BPF-induced cardiometabolic disease has underlying genetic risk, which can be identified using the HS rat and its founding inbred strains. We previously demonstrated that five weeks of postnatal BPF exposure significantly impacts body growth and adiposity in male HS rats. The goal of this project was to evaluate the metabolic health impact of postnatal BPF exposure in HS founding inbred strains. Weanling littermate pairs of male and female ACI/EurMcwi (ACI), BN/NHsdMcwi (BN), F344/Stm (F344), and WKY/NCrl (WKY) rats were randomly exposed to either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for ten weeks in drinking water. Cardiometabolic measures, tissues, urine, and feces were taken. Our studies determined BPF exposure in ACI female rats significantly increased feeding efficiency (0.54 ± 0.07 vs 0.62 ± 0.06 vs, p=0.04), suggesting a possible decrease in metabolic rate. BPF exposure impacted males more often than females, with ACI males showing significantly increased thyroid mass (0.045 ± 0.004 mg/g vs 0.051 ± 0.003 mg/g, p&lt;0.01), BN males showing a trend in increased pituitary mass (0.026 ± 0.003 mg/g vs 0.029 ± 0.001 mg/g, p=0.07), and WKY males showing increased adrenal mass (0.164 ± 0.010 mg/g vs 0.176 ± 0.005 mg/g, p&lt;0.01). Our preliminary data suggests that the ACI strain and male BN and WKY are susceptible to metabolic effects of BPF exposure. This work indicates that the HS rat will be a useful model for dissecting GxBPF interactions on metabolic health.

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

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.