Lílian Gonçalves Teixeira

The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

BackgroundThis study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines.MethodsMice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD).ResultsObesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group.ConclusionOur results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.

Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression☆ , ☆☆

Gluten exclusion (protein complex present in many cereals) has been proposed as an option for the prevention of diseases other than coeliac disease. However, the effects of gluten-free diets on obesity and its mechanisms of action have not been studied. Thus, our objective was to assess whether gluten exclusion can prevent adipose tissue expansion and its consequences. C57BL/6 mice were fed a high-fat diet containing 4.5% gluten (Control) or no gluten (GF). Body weight and adiposity gains, leukocyte rolling and adhesion, macrophage infiltration and cytokine production in adipose tissue were assessed. Blood lipid profiles, glycaemia, insulin resistance and adipokines were measured. Expression of the PPAR-α and γ, lipoprotein lipase (LPL), hormone sensitive lipase (HSL), carnitine palmitoyl acyltransferase-1 (CPT-1), insulin receptor, GLUT-4 and adipokines were assessed in epidydimal fat. Gluten-free animals showed a reduction in body weight gain and adiposity, without changes in food intake or lipid excretion. These results were associated with up-regulation of PPAR-α, LPL, HSL and CPT-1, which are related to lipolysis and fatty acid oxidation. There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ. Moreover, intravital microscopy showed a lower number of adhered cells in the adipose tissue microvasculature. The overexpression of PPAR-γ is related to the increase of adiponectin and GLUT-4. Our data support the beneficial effects of gluten-free diets in reducing adiposity gain, inflammation and insulin resistance. The data suggests that diet gluten exclusion should be tested as a new dietary approach to prevent the development of obesity and metabolic disorders.

Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation.

BACKGROUND & AIMS Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action. METHODS AND RESULTS ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1β and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit. CONCLUSION Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.

Modulation of adipose tissue inflammation by FOXP3+ Treg cells, IL-10, and TGF-β in metabolically healthy class III obese individuals

OBJECTIVE The objective of this study was to compare the profiles of proinflammatory (interleukin [IL]-6 and tumor necrosis factor [TNF]) and anti-inflammatory (IL-10 and transforming growth factor [TGF]-β) adipokines in the blood, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) of metabolically healthy class III obese individuals and normal-weight controls. METHODS The serum concentrations (enzyme-linked immunosorbent assay [ELISA]), mRNA expression levels (reverse transcriptase polymerase chain reaction), and adipose tissue secretion (ELISA) of IL-6, TNF, IL-10, and TGF-β were analyzed, as were the mRNA expression of FOXP3 (present in regulatory T cells) and the secretion (Western blotting) of matrix metalloproteinases in the adipose tissue. RESULTS There were no differences in the circulating levels, expression, or secretion of IL-6 and TNF between the groups or tissues. The expression and circulating levels of IL-10 were higher in obese individuals, especially in the SAT. Although the blood concentration of TGF-β was similar between the groups, its expression and secretion levels were higher in the adipose tissues of obese individuals compared with controls. FOXP3 and MMP expression levels were higher in the SAT and VAT of obese individuals, respectively, compared with the controls. CONCLUSION Metabolically healthy, extremely obese individuals have effective immunoregulation to counter chronic obesity-related inflammation through the increased production of the anti-inflammatory cytokines IL-10 and TGF-β in adipose tissue, especially SAT; the increased presence of FOXP3-positive regulatory T cells; and increases in angiogenesis and adipogenesis induced by TGF-β and MMPs. These regulatory mechanisms could be important in the delayed onset of metabolic complications, even in extremely obese individuals.

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr−/−, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

Beneficial effects of L-arginine on immune responses and bowel function have been reported. Mucositis is a side effect of chemotherapy treatment that affects approximately 40% of patients. This complication is characterized by inflammation that affects the gastrointestinal tract, increasing permeability and causing abdominal pain, nausea, vomiting, and diarrhea, which worsen the patients nutritional status and increases morbimortality. The aim of this study was to evaluate the effect of pretreating with 2% L-arginine supplementation in water on mucositis as induced by 5-fluorouracil (5-FU; a single dose of 200 mg/kg body weight) in Swiss male mice. The effect of L-arginine on weight, intestinal permeability, morphology, and the histopathological score of the small intestine (from 0 to 12), oxidative stress, myeloperoxidase (MPO), and N-acetylglucosaminidase (NAG) activities were evaluated. Intestinal length improvement was observed, in addition to the partial recovery of the mucosal architecture. L-arginine attenuated the histopathological score and MPO activity. There was also an improvement in intestinal permeability, despite weight loss after 5-FU administration. In conclusion, L-arginine can positively impact intestinal mucositis by promoting partial mucosal recovery, reducing inflammation and improving intestinal permeability.

Differences in adipose tissue inflammation and oxidative status in C57BL/6 and ApoE-/- mice fed high fat diet.

Apolipoprotein E deficient (Apo E-/-) mice are more resistant to the development of obesity compared to C57BL/6 wild type mice. They also hold a high basal oxidative status due to the loss of antioxidant action of apolipoprotein E. Since obesity is also an inducer of inflammation, we studied the effect of high-fat diet on obesity and oxidative stress in C57BL/6 and Apo E-/- mice for 9 weeks. The results confirmed that Apo E-/- mice fed high-fat diet are more resistant to the increase of both body weight and adiposity compared to C57BL/6 mice. Despite this, Apo E-/- mice presented a higher basal oxidative stress that was enhanced by high-fat diet. Macrophage infiltration, macrophage forming crown-like structures and proinflammatory adipokines (interleukin 6 and tumor necrosis factor alpha) were all higher in adipose tissue from Apo E-/- compared to C57BL/6 mice, regardless of diet type. In conclusion, although Apo E-/- mice are more resistant to becoming obese, they develop more severe adipose tissue inflammation companied by its consequences.

Kefir Supplementation Improves Lipid Profile and Oxidative Stress but does not Reduce Atherosclerotic Lesion in apoE Deficient Mice

Kefir Supplementation Improves Lipid Profile and Oxidative Stress but does not Reduce Atherosclerotic Lesion in apoE Deficient Mice Cardiovascular diseases are related to several risk factors, and diet and life style modifications are among the targets of the treatment and prevention. Consequently, natural compounds that act as protective agents are continuously studied. In this context, kefir solutions have been proposed as a potential adjuvant of treatment, since some studies showed its role in reducing oxidative stress, and blood lipids. The present study investigated the effects of brown sugar-fermented kefir solution on the associate risk factor and development of atherosclerosis.

White tea (Camellia sinensis) extract reduces oxidative stress and triacylglycerols in obese mice

White tea is an unfermented tea made from young shoots of Camellia sinensis protected from sunlight to avoid polyphenol degradation. Although its levels of catechins are higher than those of green tea (derived from the same plant), there are no studies addressing the relationship between this tea and obesity associated with oxidative stress.The objective of this study was to evaluate the effect of white tea on obesity and its complications using a diet induced obesity model. Forty male C57BL/6 mice were fed a high-fat diet to induce obesity (Obese group) or the same diet supplemented with 0.5% white tea extract (Obese + WTE) for 8 weeks. Adipose tissue, serum lipid profile, and oxidative stress were studied. White tea supplementation was not able to reduce food intake, body weight, or visceral adiposity. Similarly, there were no changes in cholesterol rich lipoprotein profile between the groups. A reduction in blood triacylglycerols associated with increased cecal lipids was observed in the group fed the diet supplemented with white tea. White tea supplementation also reduced oxidative stress in liver and adipose tissue. In conclusion, white tea extract supplementation (0.5%) does not influence body weight or adiposity in obese mice. Its benefits are restricted to the reduction in oxidative stress associated with obesity and improvement of hypertriacylglycerolemia.

Sodium butyrate modulates adipocyte expansion, adipogenesis, and insulin receptor signaling by upregulation of PPAR-γ in obese Apo E knockout mice

OBJECTIVES Studies suggest that sodium butyrate reduces obesity-associated inflammation and insulin resistance in in vitro and in vivo models. Apo E-/- mice have high basal oxidative stress and naturally develop dyslipidemia and atherosclerosis. Because these disorders are present in obesity, the aim of this study was to determine whether Apo E-/- mice could be a more realistic model for studying obesity and insulin resistance. METHODS We evaluated the action of orally administered sodium butyrate on adipose tissue expansion and insulin resistance using diet-induced obese Apo E-/- mice. RESULTS Findings from the present study demonstrated that obese mice fed a sodium butyrate-supplemented diet presented a modest reduction of weight gain associated with reduction of adipocyte expansion, induction of adipogenesis and angiogenesis, and adiponectin production. Sodium butyrate also improved insulin sensitivity, by increasing insulin receptor expression associated with activation of Akt signaling pathway. These results were associated with increased peroxisome proliferator-activated receptor-γ expression and nuclear factor-κB downregulation. CONCLUSION These results suggested that oral supplementation of butyrate could be useful as an adjuvant in the treatment of obesity, metabolic syndrome, and insulin resistance.