Rat Adipose Tissue Research Articles

Changes of LRP6/β-catenin pathway in adipose tissue of rats with intrauterine growth restriction with catch-up growth.

To investigate the expression of low-density lipoprotein receptor-related protein 6 (LRP6)/β-catenin pathway related proteins in adipose tissue of rats with intrauterine growth restriction with catch-up growth SD rats were randomly divided into nutrition-restriction rats and normal feed rats during pregnancy. CG-IUGR model was established by reducing the number of offspring in the nutrition-restriction rats (CG-IUGR group); while the rats in the control group were offspring of the normal feed pregnant rats. In order to exclude the interference of gender, male offspring mice were selected in both the CG-IUGR group and the control group in the following studies. The CG-IUGR group and the control group were subjected to glucose tolerance test at 12 weeks of age, and the perirenal adipose tissue samples were taken to observe the adipose structure by HE staining. Expression of LRP6, β-catenin and insulin receptor substrate 1 (IRS-1) in adipocytes were examined by confocal microscopy. Protein expression of LRP6, β-catenin and IRS-1 were measured by Western blotting. Blood glucose level and the area under the cure of CG-IUGR group were significantly higher than that of control group (both <0.05). Adipocyte size in the CG-IUGR group was significantly larger than that of control group, and the expression of LRP6, β-catenin and IRS-1 protein in adipose tissue of the CG-IUGR group was significantly lower than that of control group (all <0.05). : The expression of LRP6/β-catenin pathway related proteins is reduced in the adipose tissue in CG-IUGR rats, probably contributing to the insulin resistance in these rats.

Effect of Nitrate on Gene and Protein Expression of Nitric Oxide Synthase Enzymes in Insulin-Sensitive Tissues of Type 2 Diabetic Male Rats

Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of type 2 diabetes mellitus (T2DM). This study aims to determine the effects of nitrate (NO3 -) on gene and protein expression of NO synthase (NOS) enzymes in the liver, soleus muscle (SM), and epididymal adipose tissue (eAT) of rats with T2DM. Twenty-eight male rats were divided into 4 groups: Control, diabetes, control+NO3 -, and diabetes+NO3 - (n = 7/each group). NO3 - was administered for 6 months, and mRNA and protein levels of NOS enzymes were measured at the end of the study. mRNA and protein levels of inducible NOS (iNOS) were higher in the liver (475% and 73%), SM (271% and 43%), and eAT (543% and 24%) of rats with T2DM. In the case of the endothelial NOS (eNOS), diabetic rats had lower mRNA and protein levels in the liver (26% and 24%) and SM (60% and 62%) and lower mRNA level (30%) in eAT. mRNA and protein levels of neural NOS (nNOS) were lower in SM (69% and 73%) and eAT (25% and 31%) of rats with T2DM. NO3 - administration restored disrupted iNOS and eNOS expressions to their near normal values in all the studied tissues; NO3 - also increased nNOS mRNA and protein levels in SM and eAT but decreased nNOS protein level in the liver. Long-term NO3 - administration restored disrupted expression of NOS enzymes in the liver, SM, and eAT of rats with T2DM; these findings partly explain the beneficial metabolic effects of nitrate in T2DM.

Regulation of peripheral expression of glucagon-like peptide 1 receptors in a rat streptozotocin-model of sporadic Alzheimer's disease.

Our previous research indicated incretin dysregulation in a rat model of sporadic Alzheimer's disease (sAD) induced by intracerebroventricular streptozotocin (STZ-icv) and improvement of cognitive decline following oral galactose-induced potentiation of endogenous glucagon-like peptide 1 (GLP-1). This study explored peripheral GLP-1 receptors (GLP-1R) in STZ-icv rats following the acute inhibition of cerebral GLP-1 signaling and additional acute oral galactose administration. 1 month following STZ-icv treatment, male Wistar rats were acutely icv-treated with GLP-1R antagonist Exendin9-39 (85ug/kg; /EXE-icv/) (Experiment I), and 1 hour after EXE-icv additionally with D-galactose (200mg/kg, single oral dose) (Experiment II). Total/active GLP-1 levels were analyzed in plasma and cerebrospinal fluid (CSF) by ELISA. GLP-1R distribution in paraffin embedded duodenal/mesenteric adipose tissue was examined using catalyzed deposition of fluorescent reporters, and analyzed by hierarchical mixed-effect modelling. Baseline plasma level of active GLP-1 was increased in STZ-icv group (vs controls) while EXE-icv treatment decreased it in the STZ-icv and increased in the control group. In CSF, EXE-icv induced a trend of GLP-1 increment both in STZ-icv and control group. Following acute oral galactose treatment, the same trend was observed in plasma of controls, but EXE-icv didn't exhibit a reduction in STZ-icv animals, and CSF level remained unchanged in both. The GLP-1R expression in periduodenal mesenteric adipose tissue of STZ-icv rats was increased following EXE-icv but decreased following additional acute oral galactose treatment. Acute galactose treatment unmasked the effect of EXE-icv on duodenal regulation of GLP-1 as lacteal GLP-1R signal was decreased both in STZ-icv and control group following EXE-icv. Our preliminary results support the existence of dysregulated GLP-1 brain-periphery axis in the STZ-icv rat model of sAD, and additionally indicate that incretin dysregulation is localized both in the brain and the peripheral tissues of STZ-icv rats, and that brain GLP-1 seems to be involved in regulation of the peripheral GLP-1R distribution. Funded by the Croatian Science Foundation (IP-2018-01-8938). Co-financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project "Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain"; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).

The effect of mesenchymal stromal cells of various origins on mortality and neurologic deficit in acute ischemia-reperfusion in rats

Stroke is a global epidemic issue and the second leading cause of death in the world and in Ukraine. According to official statistics, every year 100-110 thousand Ukrainians suffer acute cerebrovascular disorders. One third of such patients are of working age, up to 50 % will have a disability, and only one in ten will fully return to full life. So far, promising experimental data on the treatment of neurological dysfunction using mesenchymal stromal cells (MSCs) have been obtained. The aim of study is to compare the effect of MSCs of different origins on mortality and neurologic deficit in rats with acute cerebral ischemia-reperfusion injury (CIRI). Materials and methods. Transient bilateral 20-minute occlusion of internal carotid arteries was modeled in male Wistar rats aged 4 months and animals were injected intravenously with MSCs derived from human umbilical cord Wharton's-jelly (hWJ-MSC), human and rat adipose tissue. Other groups of experimental animals were injected intravenously with rat fetal fibroblasts and cell lysate from hWJ-MSC. The last group of rats received Citicoline at a dose of 250 mg/kg as a reference drug. Control animals were injected intravenously with normal saline. The cerebroprotective effect of therapy was assessed by mortality and neurologic deficit in rats on the McGraw's stroke index score. Results. After 12 hours of observation in the crucial period in the development of experimental acute cerebrovascular disorders with the administration of hWJ-MSC, mortality was only 10 % against 45 % of animals in the control group. The use of rat fetal fibroblasts reduced the mortality of animals compare to the control group by an average of 25 %. CIRI in rats caused severe neurologic deficits: paralysis, paresis, ptosis, circling behavior. On the 7th day of observation in the control group of animals, the mean score on the McGrow's stroke index indicated severe neurological disorders. On the 14th day of observation in this group of animals there was no complete recovery of lost central nervous system functions. Compared with the control group of animals, all the treatment agents for acute CIRI (MSCs of various origins, MSC's lysate and Citicoline) contributed to a significant regression of neurologic deficit. Conclusions. Thus, transplantation of human Wharton's jelly-derived MSCs and rat fetal fibroblasts reduced mortality and alleviated neurological symptoms in rats with experimental ischemic stroke. hWJ-MSC, rat fetal fibroblasts, and rat adipose-derived MSCs reduced the incidence of neurological disorders better than Citicoline, which was accompanied by a regression of neurologic deficit dynamics on the 14th day of follow-up. The ability of stem cells of different origins to reduce neurologic deficit indicates the feasibility of their use in experimental acute cerebral ischemia.

Antidiabetic with antilipidemic and antioxidant effects of flindersine by enhanced glucose uptake through GLUT4 translocation and PPARγ agonism in type 2 diabetic rats

Ethnopharmacological relevanceMedicinal plants have been used by the people of developing countries to treat various diseases. WHO also recommends the use of medicines from plants source. In that, diabetes also one of the diseases that have been treated traditionally by several people all over the world. In India, Toddalia asiatica (L.) Lam. (Rutaceae) is also a medicinal plant used traditionally for the treatment of diabetes in Ayurveda. Moreover, T. asiatica is also used in a polyherbal formulation to treat diabetes. Aim of the studyThis study examined the antidiabetic with antilipidemic and antioxidant effects of flindersine isolated from T. asiatica leaves. Materials and methodsDiabetes was induced in Wistar rats by feeding a high-fat diet (HFD) for 15 days and injecting a single dose of 40 mg/kg b. wt. of Streptozotocin (STZ). Five days post-injection, the grouped diabetic rats were treated with 20 and 40 mg/kg of flindersine. ResultsFlindersine resulted in a clear decline of blood glucose levels during 28 days of treatment in two different doses. Flindersine also significantly (P ≤ 0.05; P ≤ 0.005) reduced the body weight gain, plasma insulin concentration, urea, creatinine, total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) levels and significantly increased (P ≤ 0.05; P ≤ 0.005) the total protein level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared to the standard drug, pioglitazone. Additionally, flindersine restored the glucose transporter protein 4 (GLUT4), adenosine monophosphate protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) expressions in adipose tissues and skeletal muscles. ConclusionIt has been found that flindersine has potent antilipidemic and antidiabetic activities by improving insulin sensitivity by enhancing the phosphorylation of AMPK, GLUT4 translocation, and PPARγ agonism on adipose tissue and skeletal muscles of diabetic rats.

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells.

Adipose tissue-derived stromal cells are promising candidates investigating the stem cell-related treatment. However, their proportion and utility in the human body decline with time, rendering stem cells incompetent to complete repair processes in vivo. The involvement of circRNAs in the aging process is poorly understood. Rat subcutaneous adipose tissue from 10-week-old and 27-month-old rats were used for hematoxylin and eosin (H and E) staining, TUNEL staining, and circRNA sequencing. Rat adipose tissue-derived stromal cells were cultured and overexpressed with circ-ATXN2. Proliferation was examined using xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Apoptosis was induced by CoCl2 and examined using flow cytometry. RT-PCR assay and Oil Red O staining were used to measure adipogenesis at 48 h and 14 days, respectively. H and E staining showed that the diameter of adipocytes increased; however, the number of cells decreased in old rats. TUNEL staining showed that the proportion of apoptotic cells was increased in old rats. A total of 4,860 and 4,952 circRNAs was detected in young and old rats, respectively. Among them, 67 circRNAs exhibited divergent expression between the two groups (fold change ≥2, p ≤ 0.05), of which 33 were upregulated (49.3%) and 34 were downregulated (50.7%). The proliferation of circ-ATXN2-overexpressing cells decreased significantly in vitro, which was further validated by xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Overexpression of circ-ATXN2 significantly increased the total apoptotic rate from 5.78 ± 0.46% to 11.97 ± 1.61%, early apoptotic rate from 1.76 ± 0.22% to 5.50 ± 0.66%, and late apoptosis rate from 4.02 ± 0.25% to 6.47 ± 1.06% in adipose tissue-derived stromal cells. Furthermore, in circ-ATXN2-overexpressing cells, RT-PCR assay revealed that the expression levels of adipose differentiation-related genes PPARγ and CEBP/α were increased and the Oil Red O staining assay showed more lipid droplets. Our study revealed the expression profile of circRNAs in the adipose tissue of old rats. We found a novel age-related circular RNA—circ-ATXN2—that inhibits proliferation and promotes cell death and adipogenesis in rat adipose tissue-derived stromal cells.

Phactr1 negatively regulates bone mass by inhibiting osteogenesis and promoting adipogenesis of BMSCs via RhoA/ROCK2.

The imbalance between osteogenic and adipogenic differentiation of Bone marrow-derived mesenchymal stem cells (BMSCs) is involved in the occurrence and development of osteoporosis (OP). Previous studies have indicated the potential of phosphatase and actin regulator 1 (Phactr1) in regulating osteogenic and adipogenic differentiation of BMSCs. The present study aims to investigate the function and mechanism of Phactr1 in regulating osteogenic and adipogenic differentiation of BMSCs. Herein, the expression of Phactr1 in bone and adipose tissue of OP rats was determined by immunohistochemical. BMSCs were subjected to osteogenic and adipogenic differentiation, and transfected with Phactr1 overexpression lentivirus, small interference RNA (siRNA) and KD025 (selective ROCK2 inhibitor). The relationship between Phactr1 and ROCK2 was detected by Co-IP experiment. The expression of Phactr1, Runx2, C/EBPα, RhoA and ROCK2 was detected by Western blot. Calcium nodule and lipid droplets were determined by alizarin red and Oil red O staining. Interestingly, Phactr1 increased in both bone and adipose tissue of OP rats. During osteogenic differentiation, Phactr1 decreased and active RhoA, ROCK2 increased, while overexpression Phactr1 inhibits the increase of Runx2. Phactr1 increased and active RhoA decreased, ROCK2 did not changed during adipogenic differentiation. While, Knockdown Phactr1 inhibits the increase of C/EBPα. Phactr1 and ROCK2 were combined in osteogenic differentiation, but not in adipogenic differentiation. By using KD025, the decrease of Phactr1 and increase of Runx2 were inhibited respectively in osteogenic differentiation. Meanwhile, when ROCK2 was inhibited, Phactr1, C/EBPα were significantly increased in adipogenic differentiation. These findings indicated that Phactr1 negatively regulates bone mass by inhibiting osteogenesis and promoting adipogenesis of BMSCs by activating RhoA/ROCK2.

Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation.

Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites.

Adding collagen to adipose tissue transplant increases engraftment by promoting cell proliferation, neovascularisation and macrophage activity in a rat model.

To clarify the effect of collagen addition to transplanted adipose tissue on angiogenesis, cell proliferation and tissue remodelling process and reveal whether collagen addition contributes to improving transplanted adipose tissue engraftment in rats. Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi‐quantitatively evaluated and underwent haematoxylin and eosin or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularisation. Macrophages were evaluated using flow cytometry, and the adiponectin or vascular endothelial growth factor (VEGF) mRNA was detected using real‐time polymerase chain reaction. By collagen addition to transplanted adipose tissue, higher engraftment rate semi‐quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased. In rats, adding collagen enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularisation. Therefore, collagen addition to transplanted adipose tissue could increase the engraftment rate of adipose tissue.

Celastrol attenuates high-fructose diet-induced inflammation and insulin resistance via inhibition of 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues.

High fructose consumption has been linked to low-grade inflammation and insulin resistance that results in increased intracellular 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)-induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co-administrations upon HFrD in rats and evaluate its potential to modulate 11β-HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor-kappa B (NF-κB)-driven inflammation, reduced c-Jun N-terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β-HSD1 towards oxidoreductase activity (IC50 value=4.3nM) in comparison to other HSD-related enzymes. Inhibition of 11β-HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD-induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β-HSD1 activity in adipose tissues.

Оценка биосовместимости очищенного говяжьего сухожилия на модели гетеротопической имплантации

Damage to the tendon-ligamentous apparatus places serious limitations on a personʼs physical activity. Injuries are especially common in physically healthy people leading an active lifestyle, such as athletes. To treat such injuries in orthopaedics and traumatology, autoplastic operations are performed or prostheses made of synthetic or biological materials are installed. The known treatment methods, in spite of their effectiveness, have a number of serious drawbacks, which often limit their use. Therefore, the search for new approaches and materials for plastic ligaments is an urgent task. Today, biotissue prostheses are accumulating advantages over their synthetic counterparts. The most promising raw material for biological ligament prostheses, due to its availability in the required quantity and optimal size, is the flexor and extensor calf tendons. This paper aimed to develop a method for treating xenogenic tendon to manufacture ligament prostheses and assessing its biocompatibility in a heterotopic implantation model. To manufacture a ligament prosthesis, the raw material was subjected to mechanical cleaning and chemical-physical treatment, as well as treatment with supercritical carbon dioxide fluid with the addition of the nonionic surfactant Tween 80, which together contributed to effective decellularization and removal of other biologically active components, while maintaining the physical and mechanical parameters and natural fiberarchitectonics of native raw materials. The biocompatible properties of ligament prosthesis specimens made from the flexor and extensor calf tendons using this method were evaluated in a model of heterotopic implantation into the subcutaneous adipose tissue of rats. The results obtained confirm the promising use of this material, treated according to the proposed method, in clinical practice.

Effects of sago starch on body weight, food intake, caecum short chain fatty acids, adipose tissue, and hepatic lipid content of fat-induced Sprague Dawley rats

Sago starch which naturally contains high amount of resistant starch, comes to the attention due to its ability to confer health benefits as functional food i.e., prebiotic. The present work aimed to investigate the effects of sago starch consumption on body weight, satiation, caecum short chain fatty acids body, and hepatic lipid content on diet-induced obese rats for obesity management. A total of 36 male Sprague Dawley rats were fat-induced and divided into the obesity-prone and obesity-resistant groups. Eight percent and sixteen percent resistant starch from sago and Hi-maize260 were incorporated into the standardised feed formulation. Food intake was weighed throughout the intervention period. The caecum sample was subjected to short chain fatty acids analysis using HPLC. Hepatic lipid content was measured using the Folch method. Both dosages of sago starch (8 and 16% SRS) promoted body weight loss with a reduction of food intake, which suggested satiety. No significant differences was observed in the production of lactate, acetate, propionate, and butyrate from the caecum sample. Both dosages of sago starch (8 and 16% SRS) also showed lower hepatic lipid content and visceral adipose tissue than the baseline and control groups. However, 8% sago starch showed the lowest hepatic lipid content in obesity-prone and obesity-resistant groups. Overall results demonstrated that sago starch has the potential as an obesity and overweightness control regime as it promotes satiety, lowers visceral adipose tissue, and reduces hepatic lipid content. Consumers should consider adding sago starch in their daily meals.

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.

Lean in one way, in obesity another: effects of moderate exercise in brown adipose tissue of early overfed male Wistar rats.

Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO2max achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (pPO < 0.0001) and -off (pPO < 0.01). Exercise increased BAT temperature in lights-on (pExe < 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (pExe < 0.05), β3-AR (pExe < 0.001), and UCP1 (pExe < 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (pExe < 0.0001) with greater effect in increasing UCP1 (pExe < 0.001) and increased β3-AR (pExe < 0.001) content. Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased β3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.

Liraglutide may affect visceral fat accumulation in diabetic rats via changes in FTO, AMPK, and AKT expression

PurposeThe aim of this study is to explore the effects of liraglutide (LRG) on the expression of FTO, AMPK, and AKT in the visceral adipose tissues of obese and diabetic rats and the underlying mechanisms thereof.MethodsThirty SPF-grade, male SD rats were randomly divided into the healthy control, diabetic model (DM), and DM + LRG groups. The DM and DM + LRG groups were administered normal saline and LRG (0.6 mg/kg/d), respectively. After 12 weeks, the body weight of the rats was measured, and their visceral adipose tissues were collected and weighed; the levels of serum biochemical indicators and FTO, AMPK, and AKT in these tissues were then measured using qRT-PCR and western blotting.ResultsCompared to the control group, the body weight and visceral fat accumulation and blood glucose, TG, TC, and LDL-C levels increased significantly, while the HDL-C levels decreased significantly, in the DM group (p < 0.05). After LRG treatment, the HDL-C levels increased significantly, but the levels of the other indicators decreased significantly (p < 0.05). Compared to the control group, the visceral adipose tissue levels of FTO and AKT increased significantly, while the AMPK levels decreased significantly in the DM group (p < 0.05). After LRG treatment, the FTO and AKT levels decreased significantly, and the AMPK levels increased significantly (p < 0.05).ConclusionLRG may activate and inhibit the AMPK and AKT pathways, respectively, and decrease FTO expression, thereby alleviating abdominal obesity in type 2 diabetes.

Dietary lysine restriction induces lipid accumulation in skeletal muscle through an increase in serum threonine levels in rats

We previously reported that dietary amino acid restriction induces the accumulation of triglycerides (TAG) in the liver of growing rats. However, differences in TAG accumulation in individual cell types or other tissues were not examined. In this study, we show that TAG also accumulates in the muscle and adipose tissues of rats fed a low amino acid (low-AA) diet. In addition, dietary lysine restriction (low-Lys) induces lipid accumulation in muscle and adipose tissues. In adjusting the nitrogen content to that of the control diet, we found that glutamic acid supplementation to the low-AA diet blocked lipid accumulation, but supplementation with the low-Lys diet did not, suggesting that a shortage of nitrogen caused lipids to accumulate in the skeletal muscle in the rats fed a low-AA diet. Serum amino acid measurement revealed that, in rats fed a low-Lys diet, serum lysine levels were decreased, while serum threonine levels were significantly increased compared with the control rats. When the threonine content was restricted in the low-Lys diet, TAG accumulation induced by the low-Lys diet was completely abolished in skeletal muscle. Moreover, in L6 myotubes cultured in medium containing high threonine and low lysine, fatty acid uptake was enhanced compared with that in cells cultured in control medium. These findings suggest that the increased serum threonine in rats fed a low-Lys diet resulted in lipid incorporation into skeletal muscle, leading to the formation of fatty muscle tissue. Collectively, we propose conceptual hypothesis that “amino-acid signal” based on lysine and threonine regulates lipid metabolism.

Polar fraction from Parkinsonia aculeata aerial parts extract improves imbalanced metabolic profile and reduces proinflammatory interleukin levels in white adipose tissue in obese rats induced by western diet

Ethnopharmacological relevanceParkinsonia aculeata L. (Cesalpineaceae) is a medium tree found in the Xingó region (semi-arid area) in Northeast of Brazil, recognised by local population as an antidiabetic agent. According information from local community, the commonly traditional preparation is prepared as an infusion of the aerial part of the plant and consumed over the day to manage diabetes-related complications. Previous studies have described Parkinsonia aculeate as a product with both hypoglycemic and hypotriglyceridemic effects. Aim of the studyThe objective of this study was to evaluate the effects of polar fraction obtained from the hydroethanolic extract of Parkinsonia aculeata (PfrHEPA) on the lipid profile of animals that consumed a westernized diet. Materials and methodsThirty-six Wistar rats (45–55 g) were fed either with standard control(C) or westernized diet(W) for 120 days. The food intake, body weight evolution and body size were also analyzed. From 120 to 150 days, they were orally treated according to their group with vehicle (distillated water, 10 mL/kg), PfrHEPA at three doses (35, 70 and 140 mg/kg/day) or Gemfibrozil (140 mg/kg/day) for 30 days. ResultsThe animals fed with westernized diet showed dyslipidemia when compared to animals receiving a standard diet. Treatment with PfrHEPA (140 mg/kg), even with the continued consumption of westernized diet by animals (from 120 to 150 days) promoted a significant reduction in total cholesterol, LDL and triglyceride levels, in relation to untreated W group. PfrHEPA 140 mg/kg reduced the key serum lipids and glycaemia as well as inflammatory cytokines known as important risk factors of cardiovascular diseases. ConclusionsThe observed evidence may contribute to the control of metabolic parameters as dyslipidemia corroborating the ethnopharmacological information concerning the antihyperlipidemic and hypoglycemic activities of P. aculeata.

Investigation of d-allulose effects on high-sucrose diet-induced insulin resistance via hyperinsulinemic-euglycemic clamps in rats

d-Allulose, a C-3 epimer of d-fructose, is a rare sugar that has no calories. Although d-allulose has been reported to have several health benefits, such as anti-obesity and anti-diabetic effects, there have been no reports evaluating the effects of d-allulose on insulin resistance using a hyperinsulinemic-euglycemic clamp (HE-clamp). Therefore, we investigated the effects of d-allulose on a high-sucrose diet (HSD)-induced insulin resistance model. Wistar rats were randomly divided into three dietary groups: HSD containing 5% cellulose (HSC), 5% d-allulose (HSA), and a commercial diet. The insulin tolerance test (ITT) and HE-clamp were performed after administration of the diets for 4 and 7 weeks. After 7 weeks, the muscle and adipose tissues of rats were obtained to analyze Akt signaling via western blotting, and plasma adipocytokine levels were measured. ITT revealed that d-allulose ameliorated systemic insulin resistance. Furthermore, the results of the 2-step HE-clamp procedure indicated that d-allulose reversed systemic and muscular insulin resistance. d-Allulose reversed the insulin-induced suppression of Akt phosphorylation in the soleus muscle and epididymal fat tissues and reduced plasma TNF-α levels. This study is the first to show that d-allulose improves systemic and muscle insulin sensitivity in conscious rats.

Effects of Cinnamon Extract Consumption and Swimming Exercise on the Expression of ATGL and CGI-58 in the Visceral Adipose Tissue of Streptozotocin-induced Diabetic Rats

Introduction: Diabetes is a widespread disease, and various techniques are used for its prevention, control, and treatment, including physical exercises and medicinal herbs. Natural medicines and exercise are comparatively inexpensive and cause fewer complications compared to chemical drugs. The present study aimed to evaluate the effects of a swimming course and cinnamon extract consumption on the expression of adipose triglyceride lipase and CGI-58 in the visceral adipose tissue of streptozotocin-induced diabetic rats. Methods: This experimental study was conducted on 28 diabetic rats, which were randomly divided into four groups of seven, including 1) control (C),2) cinnamon use (Ci),3) swimming course(S), and 4) cinnamon extract with swimming (S+Ci). The animals received the intended treatment for six weeks in packs of three and four and five classes per week, while the rats in groups two and four received 200mg/kg of cinnamon orally every day for six weeks. Data analysis was performed using the one-way analysis of variance (ANOVA) and Tukey�s post-hoc test at the significance level of P�0.050. Results: The results of ANOVA indicated that ATGL gene expression in the S (P=0.04) and S+Ci groups (P=0.0001) was significantly higher than the control group. In addition, ATGL gene expression in the S group (P=0.0006) was higher compared to the Ci group, while it was significantly higher in the S+Ci group (P=0.0001) compared to the Ci and S groups. CGI-58 gene expression in the S+Ci group (P=0.0001) was also significantly higher than the control, S, and Ci groups, while it was significantly higher in the S group (P=0.036) compared to the Ci group. Conclusion: According to the results, swimming exercise and cinnamon extract consumption increased the expression of CGI-58 and ATGL protein in the diabetic rats. Therefore, it seems that CGI-58 plays a key role in the activation of lipolysis by ATGL, and higher CGI-58 could increase ATGL, which ultimately accelerates the lipolysis process, reduces fat, and improves insulin resistance in the visceral adipose tissue.

The Effect of Hyperbaric Therapy on Brown Adipose Tissue in Rats

Brown adipose tissue (BAT) plays an important role in thermogenic regulation, which contributes to alleviating diet-induced obesity through uncoupling protein 1 (UCP1) expression. While cold exposure and physical exercise are known to increase BAT development and UCP1 expression, the contribution of hyperbaric oxygen (HBO) therapy to BAT maturation remains largely unknown. Here, we show that HBO treatment sufficiently increases BAT volumes and thermogenic protein levels in Sprague-Dawley rats. Through 18F-FDG PET/CT analysis, we found that exposure to high-pressure oxygen (1.5–2.5 ATA) for 7 consecutive days increased radiolabeled glucose uptake and BAT development to an extent comparable to cold exposure. Consistent with BAT maturation, thermogenic protein levels, such as those of UCP1 and peroxisome proliferator-activated receptor γ coactivator 1α (PGC−1α), were largely increased by HBO treatment. Taken together, we suggest HBO therapy as a novel method of inducing BAT development, considering its therapeutic potential for the treatment of metabolic disorders.