Role of IL-18 in adipose tissue remodeling and metabolic dysfunction.

BACKGROUND/OBJECTIVES: Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism. MATERIALS/SUBJECTS AND METHODS: We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18-/-) male mice fed a chow diet and samples from bariatric surgery patients. RESULTS: IL-18-/- mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice's fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression. CONCLUSIONS: IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.

Protective Effect of Bovine Milk Extracellular Vesicles on Alveolar Bone Loss.

SCOPE: Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. METHODS AND RESULTS: This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. CONCLUSION: Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.

High resting energy expenditure in women with episodic migraine: exploring the use of predictive formulas.

Introduction: Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans' Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients. Methods: This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without (controls). We collected clinical, demographic, and anthropometric data. Migraine severity was measured using the Migraine Disability Test and Headache Impact Test, version 6. The REE was measured by indirect calorimetry, and it was compared with the predicted REE calculated by formulas. Results: Patients with migraine had higher REE when compared to controls (p < 0.01). There was a positive correlation between REE and the patient-reported number of migraine attacks per month (Rho = 0.226; p = 0.044). Mifflin-St Jeor and Henry and Rees were the predictive formulas that have more accuracy in predicting REE in women with migraine. Discussion: Considering the benefits of nutritional interventions on treating migraines, accurately measuring REE can positively impact migraine patient care. This study enhances our understanding of the relationship between pain and energy expenditure. Our results also provide valuable insights for healthcare professionals in selecting the most effective predictive formula to calculate energy expenditure in patients with migraine.

Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice.

OBJECTIVES: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. METHODS: Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. RESULTS: In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480- was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. CONCLUSIONS: These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.

Eosinophils protect from metabolic alterations triggered by obesity.

BACKGROUND: Eosinophils are generally related to helminth infections or allergies. Their association with metabolic alterations and adipose tissue (AT) remodeling has been demonstrated mainly in animal models of obesity. However, their physiological role in driving metabolic features has not yet been well described. Herein, we aimed to evaluate the participation of eosinophils in metabolic and adipose tissue homeostasis in mice and humans, focusing on a translational perspective. MATERIAL AND METHODS: Male BALB/c wild-type (WT) mice and GATA-1 knockout (Δdb/GATA-1-/-) mice were followed until 16-week-age in a regular diet or were fed with a high-refined-carbohydrate (HC) diet or high-fat (HF) diet for eight weeks. In subjects with obesity, clinical parameters and omental AT gene expression were evaluated. RESULTS: Eosinophils lack in mice fed a regular diet induced insulin resistance and increased adiposity. Their adipose tissue showed augmented cytokine levels, which could be attributed to increased leukocytes in the tissue, such as neutrophils and pro-inflammatory macrophages. Bone marrow transplant from WT mice to Δdb/GATA-1-/- mice showed some improvement in glucose metabolism with lower adipose tissue mass accretion. Upon an unhealthy diet challenge, Δdb/GATA-1-/- mice fed HC diet showed a mild degree of adiposity and glucose metabolic dysfunction severe in those mice fed HF diet. The expression of eosinophil markers in omental AT from humans with severe obesity was positively correlated to eosinophil cytokines and insulin sensitivity surrogate markers and negatively correlated to systemic insulin, HOMA-IR, and android fat mass. CONCLUSIONS: Eosinophils seem to have a physiological role by controlling systemic and adipose tissue metabolic homeostasis by modulating glucose metabolism, inflammation, and visceral fat expansion, even in lean mice. Indeed, eosinophils also seem to modulate glucose homeostasis in human obesity.

Effect of high-refined carbohydrate diet on intestinal integrity.

OBJECTIVES: One of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes. METHODS: Male BALB/c mice were fed a chow or an HC diet for 8 wk. RESULTS: Although differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation. CONCLUSION: Metabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity.

The Intervention of Diet on Energy Metabolism.

Food intake patterns determine changes in energy expenditure due to their influence on body size and composition (percentage of fat, bone, and muscle), which can modulate signaling pathways that optimize energy consumption [...].

Decreased plasma levels and dietary intake of minerals in women with migraine.

It has been suggested that an imbalance in mineral levels is involved in the pathophysiology of migraine. However, only a few studies have investigated the circulating levels of mineral in patients with migraine during the pain-free period (i.e. interictal). This study aimed to investigate whether the interictal plasma levels of minerals of women with migraine differ from those of women without migraine (controls). This is a cross-sectional study involving 67 women, of which 38 were diagnosed with migraine and 29 were controls. The groups were similar in age and body mass index. Plasma levels of magnesium (Mg), copper (Cu), calcium (Ca), zinc (Zn), iron (Fe), and selenium (Se) were measured. Dietary intake was assessed using a 24-hour food recall, and migraine impact was evaluated using the Headache Impact Test, version 6 (HIT-6). The association between migraine disability, and plasma levels and dietary intake of minerals was assessed through correlation and logistic regression analyses. Women with migraine had significantly lower plasma levels of Mg, Ca, Cu, and Zn than controls. In parallel, dietary intake of Mg, Cu, and Fe was significantly lower in patients with migraine. Migraine impact was not associated with plasma levels or dietary intake of minerals. The results suggest that patients with migraine have lower plasma levels of minerals, and dietary intervention to ensure adequate mineral intake should be considered as a therapeutic strategy for migraine.

Metabolic and behavioral effects of time-restricted eating in women with overweight or obesity: Preliminary findings from a randomized study.

OBJECTIVES: The aim of this study was to evaluate the effects of 8 wk of time-restricted eating (TRE) along with a caloric restriction on metabolic profile, metabolic rate, symptoms of mood, and eating disorders and weight loss in women with overweight or obesity. METHODS: Women age 18 to 59 y with a body mass index of ≥25 kg/m2 were enrolled in this parallel-arm, randomized, clinical trial. Participants were randomly allocated into two groups (8-h TRE or non-TRE group) using a 2:1 allocation strategy. Both groups received a diet plan with caloric restriction. Body weight, resting metabolic rate, metabolic profile, and symptoms of mood and eating disorders were evaluated at baseline and on follow up. RESULTS: Thirty-six subjects were included in this study, with 24 in the TRE group and 12 in the non-TRE group. Subject in the TRE group showed more pronounced loss of weight, body fat mass, and fat-free mass than those in the non-TRE group. These losses were not associated with changes in resting metabolic rate, metabolic profile, and eating or mood disorder symptoms. CONCLUSIONS: This study showed that 8 wk of TRE does not influence behavioral parameters in individuals with overweight or obesity, but could lead to weight loss.

Dysbiotic oral microbiota contributes to alveolar bone loss associated with obesity in mice.

INTRODUCTION: Periodontal diseases (PD) are inflammatory conditions that affect the teeth supporting tissues. Increased body fat tissues may contribute to activation of the systemic inflammatory response, leading to comorbidities. Some studies have shown that individuals with obesity present higher incidence of PD than eutrophics. OBJECTIVE: To investigate the impact of obesity on periodontal tissues and oral microbiota in mice. METHODOLOGY: Two obesity mice models were performed, one using 12 weeks of the dietary protocol with a high-fat (HF) diet in C57BL/6 mice and the other using leptin receptor-deficient mice (db/db-/-), which became spontaneously obese. After euthanasia, a DNA-DNA hybridization technique was employed to evaluate the microbiota composition and topical application of chlorhexidine (CHX), an antiseptic, was used to investigate the impact of the oral microbiota on the alveolar bone regarding obesity. RESULTS: Increased adipose tissue may induce alveolar bone loss, neutrophil recruitment, and changes in the oral biofilm, similar to that observed in an experimental model of PD. Topical application of CHX impaired bone changes. CONCLUSION: Obesity may induce changes in the oral microbiota and neutrophil recruitment, which are associated with alveolar bone loss.

Contribution of RAS, ROS and COX-1-derived prostanoids to the contractile profile of perivascular adipose tissue in cafeteria diet-induced obesity.

AIMS: Obesity can lead to the loss of the anticontractile properties of perivascular adipose tissue (PVAT). Given that cafeteria (CAF) diet reflects the variety of highly calorie and easily accessible foods in Western societies, contributing to obesity and metabolic disorders, we sought to investigate the impact of CAF diet on PVAT vasoactive profile and the involvement of renin-angiotensin system, oxidative stress, and cyclooxygenase pathway. MAIN METHODS: Male Balb/c mice received standard or CAF diet for 4 weeks. Oral glucose tolerance and insulin sensitivity tests were performed, and fasting serum glucose, cholesterol and triglyceride parameters were determined. Vascular reactivity, fluorescence and immunofluorescence analyzes were carried out in intact thoracic aorta in the presence or absence of PVAT. KEY FINDINGS: CAF diet was effective in inducing obesity and metabolic disorders, as demonstrated by increased body weight gain and adiposity index, hyperlipidemia, hyperglycemia, glucose intolerance and insulin insensitivity. Importantly, CAF diet led to a significant decrease in aortic contractility which was restored in the presence of PVAT, exhibiting therefore a contractile profile. The contractile effect of PVAT was associated with the activation of AT1 receptor, reactive oxygen species, cyclooxygenase-1, thromboxane A2 and prostaglandin E2 receptors. SIGNIFICANCE: These findings suggest that the contractile profile of PVAT involving the renin-angiotensin system activation, reactive oxygen species and cyclooxygenase-1 metabolites may be a protective compensatory adaptive response during early stage of CAF diet-induced obesity as an attempt to restore the impaired vascular contraction observed in the absence of PVAT, contributing to the maintenance of vascular tone.

Ginger supplementation does not increase energy expenditure in female adults.

Food components with thermogenic properties are promising antiobesity agents. Ginger (Zingiber officinale Rosc.) bioactive compounds have a capsaicin-like vanillyl portion, which has been attributed to thermogenic effect in previous experimental studies. However, studies conducted in humans have evaluated only the acute thermogenic effect of ginger, and demonstrated contradictory results. We evaluated the effect of long-term consumption of dry ginger extract on the resting energy expenditure (REE) of female adults with high body adiposity. METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (NCT02570633). Participants age 18 to 60 y were randomly assigned into two groups: Intervention (600 mg of ginger extract daily) and placebo (cellulose). The intervention lasted 3 mo. Anthropometric measurements, blood pressure, and REE were assessed at each visit. RESULTS: A total of 66 female participants with high body adiposity were included in the analysis (mean age: 29 y [range, 20-55 y]; body mass index: 23.3 ± 2.7), with 30 participants in the ginger group and 36 in the placebo group. There were no significant differences in baseline characteristics between the groups. No differences were observed for group × time interaction on REE. Body composition and blood pressure followed the same pattern (all P > 0.05). CONCLUSIONS: Ginger extract consumption for 3 mo did not change the REE, anthropometric, and clinical data of female adults with excess adiposity.

Protective Effect of Virgin Coconut Oil on Osteopenia Induced by High Refined Carbohydrate-Containing Diet in Mice.

BACKGROUND: Obesity leads to chronic low-grade inflammation, promoting detrimental effects on bone. The consumption of virgin coconut oil (VCO) is associated with benefits related to meta-inflammation. We evaluated the effect of VCO supplementation on osteopenia promoted by diet-induced obesity in mice. METHODS: Male BALB/c mice were fed a control (C) or highly refined carbohydrate-containing (HC) diet for eight weeks. After that, the HC diet group was supplemented with three doses of VCO for four weeks. RESULTS: The HC diet increased the adiposity and leptin levels associated with augmented systemic inflammatory cells improved with VCO supplementation. The HC diet reduced the trabecular bone in the tibia, lumbar vertebrae, distal and proximal femur, as well as the bone mineral density of the femur and alveolar bone. The VCO supplementation reverted bone osteopenia by increasing the trabecular bone in different sites and improving femur and alveolar bone microarchitecture. Although the reduced number of osteoblasts in the alveolar bone of the HC diet group was not significantly enhanced by VCO supplementation, the reduced Alp expression in the HC diet group was enhanced in the VCO group. These beneficial effects were associated with lowering the Rankl/Opg ratio. CONCLUSION: VCO supplementation might be an effective strategy to attenuate bone osteopenic effects induced by obesity.

Cannabidiol ameliorates the anxiogenic and compulsive-like behaviors induced by chronic consumption of a high-carbohydrate diet in male mice.

The excessive consumption of ultra-processed foods and the development of obesity has been associated with several comorbidities, including psychiatric disorders. Excess fat tissue promotes a low-intensity inflammatory state, mainly in the white tissue, which is essential in developing metabolic alterations and influences brain homeostasis. In this scenario, Cannabidiol (CBD), a compound from Cannabis sativa, has presented anxiolytic and anti-inflammatory effects in murine models. This study verified whether CBD treatment would ameliorate the compulsive-like and anxiety-like behaviors observed after mice's chronic consumption of a high-refined carbohydrate (HC) diet. BALB/c male mice received a control or HC diet for 12 weeks followed by vehicle and CBD (30 mg/Kg, i.p.) administration, and their behavior was evaluated in the Marble Burying test (MB) and Novel Suppressing Feeding test (NSF). The sub-chronic, but not acute, treatment with CBD attenuated the compulsive-like and anxiogenic-like behavior induced by the HC diet. Our data reinforced the harmful effects of the HC diet's chronic consumption on compulsive and anxious behaviors and the potential of CBD as a drug treatment for psychiatric disorders associated with obesity.

Mindfulness-based program to support lifestyle modification and weight loss in infertile women: randomized controlled trial.

OBJECTIVE: We evaluated the short-term effects of a mindfulness-based program (MBP) on weight loss through lifestyle modification in infertile women who were overweight or obese. METHODS: The participants were randomly assigned to 8 consecutive weekly sessions of MBP plus diet or diet alone. Both groups received a customized dietary plan. Body measures were taken and a questionnaire was applied to evaluate dietary habits at baseline and three months later. RESULTS: The study was completed by 28 women in the MBP group and 24 in the control group. Body weight decreased 1.8 kg (2.1%) in the MBP group (p = 0.001, follow-up vs. baseline) and 1.7 kg (1.9%) in the control group (p = 0.035). There was an average reduction of 2.9 cm of waist circumference in the MBP group (p = 0.008) and 0.3 cm in the control group (p = 0.633). There was a significant reduction in the daily energy intake of the women attending the MBP (mean difference -430 Kcal/day, p=0.010) whereas no significant change was observed in the control group. CONCLUSION: In the short term, this MBP did not affect weight loss in infertile women, but the MBP intervention contributed to reduce waist circumference, possibly due to a significant decrease in food energy intake. TRIAL REGISTRATION NUMBER: RBR-7by76r.

Gluten-Free Diet Reduces Diet Quality and Increases Inflammatory Potential in Non-Celiac Healthy Women.

AIM: Gluten-free diets (GFDs) have gained popularity in the general population. Nonetheless, controlled studies are necessary before decisions can be made to promote GFDs. We aimed to evaluate the effects of gluten intake on body weight, body composition, and resting energy expenditure and observe the changes in nutrient intake caused by GFDs. METHODS: Twenty-three women were kept on a GFD for six weeks and received muffins with 20 g of gluten isolate (gluten period) or muffins without gluten (gluten-free period) in a crossover, single-blind, non-randomized trial. Gastrointestinal symptoms, food frequency questionnaires, body composition, and resting energy expenditure were assessed before the study (habitual or usual diet) and in the third and sixth weeks. Food intake was recorded daily for six weeks. RESULTS: Gastrointestinal symptoms, resting energy expenditure, and body weight and composition were similar during the gluten period and gluten-free period. When the diet of the gluten-free period was compared with the habitual diet, we found an increase in the intake of fat and sodium and a reduction in the intake of fiber and vitamins B1, B6, B12, and folate. The nutrient imbalance caused by a GFD led to an increase in the dietary inflammatory index, thus suggesting that this type of diet has high inflammatory potential. CONCLUSION: Gluten intake (20 g/day) did not alter body composition and resting energy expenditure in healthy women without caloric restriction in the diet for a short period (three weeks). However, a GFD led to changes in the composition of the diet, which worsened the quality of the diet and increased its inflammatory potential.

PAF signaling plays a role in obesity-induced adipose tissue remodeling.

BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS: PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS: Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.