Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects

Background: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. Methods: Blood samples were collected from 43 obese subjects (BMI ≥ 30 kg/m²) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12–18 months post-surgery and 8 healthy weight subjects (BMI 18.5–24.9 kg/m²). Monocytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were harvested after 15 h incubation. TNF-α and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. Results: TNF-α and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. Conclusion: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.     

Adipose Tissue Dysfunction in Obesity: Role of Mineralocorticoid Receptor

The mineralocorticoid receptor (MR) acts as an essential regulator of blood pressure, volume status, and electrolyte balance. However, in recent decades, a growing body of evidence has suggested that MR may also have a role in mediating pro-inflammatory, pro-oxidative, and pro-fibrotic changes in several target organs, including the adipose tissue. The finding that MR is overexpressed in the adipose tissue of patients with obesity has led to the hypothesis that this receptor can contribute to adipokine dysregulation and low-grade chronic inflammation, alterations that are linked to the development of obesity-related metabolic and cardiovascular complications. Moreover, several studies in animal models have investigated the role of MR antagonists (MRAs) in preventing the metabolic alterations observed in obesity. In the present review we will focus on the potential mechanisms by which MR activation can contribute to adipose tissue dysfunction in obesity and on the possible beneficial effects of MRAs in this setting.     

The Role of Exercise,Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue

The prevalence of obesity continues to rise worldwide despite evidence-based public health recommendations. The promise to adopt a healthy lifestyle is increasingly important for tackling this global epidemic. Calorie restriction or regular exercise or a combination of the two is accepted as an effective strategy in preventing or treating obesity. Furthermore, the benefits conferred by regular exercise to overcome obesity are attributed not only to reduced adiposity or reduced levels of circulating lipids but also to the proteins, peptides, enzymes, and metabolites that are released from contracting skeletal muscle or other organs. The secretion of these molecules called cytokines in response to exercise induces browning of white adipose tissue by increasing the expression of brown adipocyte-specific genes within the white adipose tissue, suggesting that exercise-induced cytokines may play a significant role in preventing obesity. In this review, we present research-based evidence supporting the effects of exercise and various diet interventions on preventing obesity and adipose tissue health. We also discuss the interplay between adipose tissue and the cytokines secreted from skeletal muscle and other organs that are known to affect adipose tissue and metabolism.     

Diet Quality and Bone Density in Youth with Healthy Weight,Obesity, and Type 2 Diabetes

Purpose: To assess relationships between diet quality and areal bone mineral density (aBMD) in youth with healthy weight, obesity, and type 2 diabetes (T2D). Methods: We performed a secondary analysis of cross-sectional data from youth (55% African American, 70% female) ages 10–23 years with T2D (n = 90), obesity (BMI > 95th; n = 128), or healthy weight (BMI < 85th; n = 197). Whole body (less head) areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). aBMD was expressed as age-, sex-, and ancestry-specific standard deviation scores (Z-scores). Whole body aBMD Z-scores were adjusted for height-for-age Z-score. Diet was assessed via three-day diaries, and the Healthy Eating Index (HEI) was computed. Total HEI score and HEI subcomponent scores were compared across groups, and associations with aBMD Z-scores were assessed via linear regression adjusted for group, age, sex, and ancestry. Results: Mean HEI was similar between the healthy weight, obesity, and T2D groups. Several HEI sub-components differed between groups, including meats and beans, total vegetables, milk, saturated fat, sodium, oils, and empty calories. The obesity and T2D group had significantly greater aBMD Z-scores compared to the healthy weight group. Multiple linear regression analyses revealed a significant positive association between HEI and aBMD Z-score (p < 0.05). The HEI sub-components for whole grains (p = 0.052) and empty calories (p < 0.05) were positively associated with aBMD Z-score. Conclusions: Individuals that followed a dietary pattern more closely aligned with the Dietary Guidelines for Americans had greater bone density. Since few studies have investigated the role of diet on bone in youth with obesity-related conditions, additional research is required among these populations.     

Netrin-1 Promotes Visceral Adipose Tissue Inflammation in Obesity and Is Associated with Insulin Resistance

Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.     

Glucose Handling in Morbid Obesity and the Effects of Surgically Induced Weight Loss

Morbid obesity is associated with glucose intolerance. We studied the rate of glucose turnover in 18 morbidly obese individuals and compared the results to 10 normal weight controls using the technique of the hyperglycemic clamp. Rate of glucose turnover (mg/kg/min) was defined as metabolic clearance of glucose and corresponding plasma immunoreactive insulin values were determined. The ratio of metabolic clearance of glucose to plasma insulin is a reflection of endogenous insulin sensitivity. Patients were studied again 3 months following jejunoileal bypass and gastroplasty. Fasting glucose was similar for all groups. Fasting immunoreactive insulin was 16.8 ± 5 μU/ml in preoperative obese, 4.3 ± 0.2 in controls, 6.8 ± 0.6 in postoperative jejunoileal bypass, and 6.2 ± 0.3 in postoperative gastroplasty. The difference between postoperative groups was not significant at 3 months. The jejunoileal bypass group at 1 yr gave similar results to the immediate postoperative findings. In normals the value of metabolic clearance of glucose was 3.9 ± 0.7 mg/kg/min and in the obese it was 2.05 ± 0.2 (p < 0.05). No significant improvement occurred postoperatively. Mean of the immunoreactive insulin values from 60 to 120 min was greater in preoperative obese than controls, 44.0 compared to 13.6 μU/ml (p < 0.05). A highly significant postoperative lowering occurred in both groups, jejunoileal bypass 20.7 μU/ ml, gastroplasty 22.4 μU/ml, but the difference between the surgical groups (jejunoileal and gastroplasty) is not significant. The ratio of metabolic glucose clearance to plasma insulin followed a similar pattern due primarily to the substantial decrease in insulin levels. At 1 yr after jejunoileal bypass the patients had similar findings to their immediate postoperative results. There appears to be a defect in glucose metabolism in morbidly obese individuals which does not respond to weight loss even though insulin levels drop. When the ratio of metabolic clearance of glucose to plasma insulin is compared to weight loss no correlation exists suggesting that the defect in glucose handling is not completely reversible with weight loss. (Journal of Parenteral and Enteral Nutrition 8:660–664, 1984)     

Healthy Lifestyle Intervention and Weight Loss Improve Cardiovascular Dysfunction in Children with Obesity

Background: The aim of this study was to determine the effects of a 12-month healthy lifestyle intervention based on diet plus physical activity on cardiovascular structure and function in children and adolescents with obesity; Methods: In this longitudinal study we assessed changes in anthropometric, biochemical and cardiovascular variables in 55 subjects with obesity (6–16 years) before and after a 12-month behavioral program based on Mediterranean diet plus exercise regimen. Subjects were divided in two groups based on negative change in BMI z-score ≥10% from baseline: weight losers (WL) and non-weight losers (NWL); Results: After 12 months, WL showed a significant improvement of metabolic parameters. Treatment was effective in increasing the mitral peak early diastolic velocity E and the E/A ratio. In subjects with a reduction of the number of NCEP-ATPIII metabolic syndrome criteria, lifestyle intervention reduced left ventricular area and volume. Intervention reduced carotid intima-media thickness in subjects showing a decrease of the systemic blood pressure; Conclusions: In children with obesity, cardiovascular impairment could be partially reversed by a healthy lifestyle intervention. To adopt prompt behavioral programs in childhood obesity is crucial both for prevention and treatment of precocious complications and could have an exponential impact on long-term morbidity and mortality.     

The Cultural Context of Obesity: Exploring Perceptions of Obesity and Weight Loss Among Latina Immigrants

This study used focus group methodology to examine perceptions of obesity and weight management among Latina immigrant women in Alabama. Four focus groups (N = 25) were conducted in Spanish as part of a participatory intervention development process. Participants were obese/overweight Latina immigrant women (BMI > 25) primarily recruited from a community hospital. The majority of participants were from Mexico. Participants described obesity in the context of short-term effects such as physical symptoms and aesthetics. Perceived weight gain was related to lifestyle changes since moving to the US. Social isolation, depression, and stress were reported to contribute to weight gain. Participants expressed interest in weight loss but emphasized a desire for programs that preserve traditional foods and include family. Weight-management programs designed for Latina immigrants should address their perceptions of obesity. This data also suggests that those interventions that preserve culture and incorporate family may have increased community buy-in.     

Weight Loss After Diagnosis with Gestational Diabetes and Birth Weight Among Overweight and Obese Women

To determine if, among overweight or obese women with gestational diabetes (GDM), weight loss after GDM diagnosis is associated with lower infant birth weight within levels of overweight or obesity class. Overweight and obese women with singleton pregnancies managed for GDM at a large diabetes and pregnancy program located in Charlotte, NC between November 2000 and April 2010, were eligible for this retrospective cohort study. All were managed using a rigorous standardized clinical protocol. Clinical information including maternal pre-pregnancy body mass index, gestational weight gain, treatment, and medical and obstetric history was abstracted from medical records. The association of weight loss after GDM diagnosis and birth weight was analyzed using linear regression stratified by maternal pre-pregnancy overweight or obesity class (I, II/III). Of the 322 women in this study 19 % lost weight between diagnosis of GDM and delivery. After adjustment for maternal age, parity, race/ethnicity, gestational week at first hemoglobin A1c (A1C), A1C at diagnosis, weight gain prior to GDM, treatment with insulin or oral hypoglycemic agents, gestational age at delivery, and infant sex, weight loss was associated with 238.3 g lower mean infant birth weight among overweight women (95 % CI ?393.72, ?82.95 g), but was not associated with lower mean infant birth weight among obese class II/III women (95 % CI ?275.61, 315.38 g). Weight loss, after diagnosis of GDM, is associated with lower infant birth weight among overweight women, but not among obese class II/III women.     

Relationship Between Perceptions of Obesity Causes and Weight Loss Expectations Among Adults

Objective

To examine relationships between the demographic characteristics of subjects with obesity seeking pharmaceutical-assisted weight loss and their weight loss expectations and perceptions of the causes of their obesity.

Association of Binge Eating Behavior with Total and Abdominal Adipose Tissue in a Large Sample of Participants Starting a Weight Loss or Maintenance Program

ABSTRACT

Objective: It is not clear whether binge eating (BE) behavior is associated with body composition independently of body mass index (BMI). Our aim has been to evaluate the BMI-independent contribution of BE severity and BE status on the total amount of fat mass and abdominal fat distribution in a large sample of participants.

Method: We performed a cross-sectional study among 8524 participants followed at a nutritional center. BMI and waist circumference (WC) were measured, body fat (BF) was estimated by skinfold measurement, and abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues were measured by ultrasonography. BE was assessed using the Binge Eating Scale (BES). The association between the continuous BES score (BE severity) and adiposity was assessed in the whole sample after adjustment for BMI and other confounders. The effect of BE status on adiposity was also assessed by matching binge eaters (BES ≥ 18), for sex, age, and BMI, with non-binge eaters (BES < 18).

Results: We found that 17.7% of the participants were binge eaters. Continuous BES score was associated with increasing WC (0.03 cm, 95% confidence interval [CI], 0.02 to 0.05 every 1 BES unit, p < 0.001) and decreasing BF (0.01%, 95% CI, ?0.02 to ?0.00 every 1 BES unit, p = 0.003). No association was found between BE severity and VAT and SAT. After matching, the BF of binge eaters was 0.29% (95% CI, ?0.50 to ?0.07, p = 0.01) lower than that of non-binge eaters.

Conclusions: Given the very small effect size, BE severity and status are not associated in a biologically meaningful manner with BF content and distribution.     

Relative Contribution of Gestational Weight Gain,Gestational Diabetes,and Maternal Obesity to Neonatal Fat Mass

Maternal nutritional and metabolic status influence fetal growth. This study investigated the contribution of gestational weight gain (GWG), gestational diabetes (GDM), and maternal obesity to birthweight and newborn body fat. It is a secondary analysis of a prospective study including 204 women with a pregestational body mass index (BMI) of 18.5–24.9 kg/m² and 219 women with BMI ≥ 30 kg/m². GDM was screened in the second and third trimester and was treated by dietary intervention, and insulin if required. Maternal obesity had the greatest effect on skinfolds (+1.4 mm) and cord leptin (+3.5 ng/mL), but no effect on birthweight. GWG was associated with increased birthweight and skinfolds thickness, independently from GDM and maternal obesity. There was an interaction between third trimester weight gain and GDM on birthweight and cord leptin, but not with maternal obesity. On average, +1 kg in third trimester was associated with +13 g in birthweight and with +0.64 ng/mL in cord leptin, and a further 32 g and 0.89 ng/mL increase in diabetic mothers, respectively. Maternal obesity is the main contributor to neonatal body fat. There is an independent association between third trimester weight gain, birthweight, and neonatal body fat, enhanced by GDM despite intensive treatment.     

Infancy and Childhood Obesity Grade Predicts Weight Loss in Adulthood: The ONTIME Study

We examined the relationships between intergenerational obesity, weight and size at birth, and obesity from infancy to adolescence with weight loss in response to a dietary intervention. We studied 4264 participants (3369 women; mean age 41.5 ± 12.9 years) of the ONTIME study. Participants followed a weight-loss treatment based on a Mediterranean diet. Associations between grandparental and parental obesity grade, birth weight and size, and obesity grade in infancy, childhood and adolescence with total weight loss in response to treatment were assessed, using multivariate linear regression models. A lower weight loss (kg) in response to treatment was found among participants who were obese during infancy (beta coefficient −2.13 kg; 95% CI, −3.96, −0.30; p = 0.023). Furthermore, obesity during infancy and also during childhood was associated with a slower weekly rate of weight loss during treatment (p < 0.05). In conclusion, obesity in infancy and in childhood impairs the weight-loss response to dietary treatments in adulthood. Tackling obesity throughout early life may improve the effectiveness of weight-loss interventions in adulthood.     

Piceatannol,a Dietary Polyphenol,Alleviates Adipose Tissue Loss in Pre-Clinical Model of Cancer-Associated Cachexia via Lipolysis Inhibition

Cancer-associated cachexia (CAC) is the nutrition-independent loss of lean muscle and adipose tissues, and results in reduced chemotherapy effectiveness and increased mortality. Preventing adipose loss is considered a key target in the early stages of cachexia. Lipolysis is considered the central driver of adipose loss in CAC. We recently found that piceatannol, but not its analogue resveratrol, exhibits an inhibitory effect on lipolysis. The objective of this study was to investigate the role of piceatannol in cancer-associated lipolysis and cachexia-induced weight loss. Cancer cell-induced lipolysis in adipocytes was stimulated using cancer-conditioned media (CCM) or co-culture with human pancreatic cancer cells and the cachexia-associated cytokines TNF-α and interleukin-6 in 3T3-L1 adipocytes. C26 colon carcinoma-bearing mice were modeled using CAC in vivo. Piceatannol reduced cancer-associated lipolysis by at least 50% in both CCM and cytokine-induced lipolysis in vitro. Further gene and protein analysis confirmed that piceatannol modulated the stability of lipolytic proteins. Moreover, piceatannol protected tumor-bearing mice against weight-loss in early stages of CAC largely through preserving adipose tissue, with no effect on survival. This study demonstrates the use of a dietary compound to preserve adipose in models of early stage CAC and provides groundwork for further investigation of piceatannol or piceatannol-rich foods as alternative medicine in the preservation of body fat mass and future CAC therapy.     

Sugar Intake,Obesity, and Diabetes in India

Sugar and sweet consumption have been popular and intrinsic to Indian culture, traditions, and religion from ancient times. In this article, we review the data showing increasing sugar consumption in India, including traditional sources (jaggery and khandsari) and from sugar-sweetened beverages (SSBs). Along with decreasing physical activity, this increasing trend of per capita sugar consumption assumes significance in view of the high tendency for Indians to develop insulin resistance, abdominal adiposity, and hepatic steatosis, and the increasing “epidemic” of type 2 diabetes (T2DM) and cardiovascular diseases. Importantly, there are preliminary data to show that incidence of obesity and T2DM could be decreased by increasing taxation on SSBs. Other prevention strategies, encompassing multiple stakeholders (government, industry, and consumers), should target on decreasing sugar consumption in the Indian population. In this context, dietary guidelines for Indians show that sugar consumption should be less than 10% of total daily energy intake, but it is suggested that this limit be decreased.