Strategy For Treatment Of Obesity Research Articles

Weekday time in bed and obesity risk in adolescence.

IntroductionSleep curtailment is associated with obesity in children, but few studies have investigated this relationship in a longitudinal sample of adolescents. The aim of the present study was to examine the longitudinal association between weekday time in bed (TIB) at age 10–13 and overweight at age 16–19.MethodsAdolescents and their parents (N = 3025 families), participating in a longitudinal population‐based study, completed questionnaires assessing habitual bedtime and wake time on weekdays, weight and height, socioeconomic status (SES), internalizing mental health problems and disturbed eating. Two surveys were administered with a 6‐year interval (T1 and T2). A one‐way analysis of covariance (ANCOVA) was performed examining the association between TIB and weight category 6 years later, with SES, internalizing problems and disturbed eating at baseline entered as covariates. Hierarchical and logistic regression analyses were used to assess TIB at age 10–13 years to as a predictor of body mass index (BMI) standardized deviation scores (SDS) and overweight status at age 16–19 adjusting for the same confounders and baseline BMI.ResultsA linear inverse relationship between TIB at age 10–13 and BMI category at age 16–19 was demonstrated by the ANCOVA, p < 0.001. Shorter TIB was related to higher weight, but the effect size was small (partial eta squared = 0.01). When adjusting for the included baseline confounders in the hierarchical regression model TIB significantly predicted later BMI SDS (β = −0.039, p = 0.02). The adjusted logistic regression model showed that for each hour reduction of TIB at T1 the odds of being overweight/obese at T2 increased with a factor of 1.6.ConclusionShorter TIB was found to be a significant, yet modest, independent predictor of later weight gain in adolescence. The findings implicate that establishing healthy sleep habits should be addressed in prevention and treatment strategies for adolescent obesity.

Long Term Exposure to a Grape Seed Proanthocyanidin Extract Enhances L-Cell Differentiation in Intestinal Organoids.

A grape-seed proanthocyanidin extract (GSPE) interacts at the intestinal level, enhancing glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) release, which modulate appetite and glucose homeostasis. Thus, enhancing L-cell numbers could be a strategy to promote hormone production, providing a potential strategy for obesity and type-2 diabetes mellitus (T2DM) treatment. Mice ileum organoids are used to evaluate the long-term effects of GSPE and two of its main components, epicatechin (EC) and gallic acid (GA), on intestinal differentiation. Hormone levels are determined using RIA and ELISA kits, and gene expression of transcription factors involved in intestinal cell differentiation, as well as markers of different cell types, are assessed by real-time qPCR. GSPE upregulates enterohormone gene expression and content, as well as the pan-endocrine marker chromogranin A. GSPE also modulates the temporal gene expression profile of early and late transcription factors involved in L-cell differentiation. Furthermore, GSPE upregulates goblet cell (Muc2) and enterocyte (sucraseisomaltase) markers, while downregulating stem cell markers (Lgr5+). Although EC and GA modified enterohormone release, they do not reproduce GSPE effects on transcription factor's profile. This study shows the potential role of GSPE in promoting enteroendocrine differentiation, effect that is not mediated by EC or GA.

Obesity and genetics.

Genetics is now known to play a substantial role in the predisposition to obesity and may contribute up to 70% risk for the disease. Over a hundred genes and gene variants related to excess weight have been discovered. Yet, genetic obesity risk does not always translate into actual obesity development, suggesting complex interactions between genetic, behavioral, and environmental influences and resulting epigenetic changes. Rare but serious forms of monogenic obesity typically appear in early childhood. Polygenic obesity is most common and demonstrates strong interplay between genes and the obesogenic environment. This review provides an overview of genetic causes of obesity, potential mechanisms of epigenetic changes, and environmental influences that should diminish obesity bias and offer hope for more effective obesity prevention and intervention strategies.

Lancing Drug Reservoirs into Subcutaneous Fat to Combat Obesity and Associated Metabolic Diseases.

Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self-administrable and minimally invasive transdermal drug delivery strategy for home-based long-term treatment of obesity and other diseases is developed. Specifically, ultrathin, core-shelled, and lance-shaped polymeric drug reservoirs (micro-lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet-induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core-shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity.

Bletilla striata oligosaccharides improve metabolic syndrome through modulation of gut microbiota and intestinal metabolites in high fat diet-fed mice

As traditional Chinese medicine, Bletilla striata has been widely applied to clinical treatment for its unique pharmacological profiles. This study aimed to investigate the beneficial role of Bletilla striata oligosaccharides (BO) in improving the metabolic syndrome by regulation of gut microbiota and intestinal metabolites. Treatment of HFD-fed mice with BO prevented weight gain, reversed the glucose intolerance and insulin resistance, and inhibited adipocyte hypertrophy. BO-treated mice also suppressed chronic inflammation and protected intestinal barrier from damage. These effects were linked to the reversal of gut microbiota dysbiosis, which contributed to the homeostasis of intestinal metabolites including bile acids, short-chain fatty acids and tryptophan catabolites. The depletion and reconstitution of intestinal flora from BO- or HFD-treated mice confirmed the significance of gut microbiota in regulation of HFD-induced metabolic disorders. We demonstrated for the first time that BO improved metabolic syndrome through the regulation of gut microbiota and intestinal metabolites. The modulation initiated by BO represents a promising strategy for treatment of obesity and related metabolic diseases.

Wu-Mei-Wan prevents high-fat diet-induced obesity by reducing white adipose tissue and enhancing brown adipose tissue function

BackgroundWu-Mei-Wan, a classic traditional Chinese herb medicine, is one of the most important formulations to treat digestive diseases from ancient times to the present. Our previous study showed that WMW treatment can prevent T2DM in db/db mice, which motivating the application of WMW on metabolic disorders. PurposeObesity and its comorbid diseases have increased dramatically and are now a worldwide health problem. There is still a lack of satisfactory treatment strategies for obesity. This work was designed to assess the effect and related mechanism of WMW on high fat diet (HFD)-induced obese mice model. MethodsObese mice were induced by HFD. Thetherapeutic effect of WMW were analyzed by examining body and adipose tissue weight, metabolic profile and energy expenditure. Adipose tissue phenotype was determined by histological staining and the mitochondrial content was examined by transmission electron microscopy (TEM). Immunohistochemical and immunofluorescence staining, RT-qPCR and Western blot analysis were used to evaluate expression of key molecules in adipose tissue. ResultsWMW treatment significantly protects HFD-induced obesity. Here we showed that WMW limits weight gain, improves metabolic profile and increases energy expenditure. WMW inhibits the hypertrophy and hyperplasia of white adipocytes, the mechanism involving the inhibition of TLR3/IL-6/JAK1/STAT3 pathway. In brown adipose tissue (BAT), WMW promotes thermogenicprogramme without affecting cell proliferation. The activated BMP7/ Smad1/5/9 pathway is considered to be one of the explanations for the effect of WMW on BAT. ConclusionOur results suggested that WMW can prevent obesity and its underlying mechanisms are associated with reducing white adipose tissue and enhancing brown adipose tissue function.

Combined Amelioration of Prebiotic Resveratrol and Probiotic Bifidobacteria on Obesity and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) and obesity are becoming increasingly common globally and characteristic as gut microbiota disturbance. Supplement of probiotics is considered as a promising strategy for NAFLD and obesity treatment. However, this effect varied from each other in clinical trials. We proposed that combination with a prebiotic substrate may improve the effects of probiotics. Thus, in this study, we investigated the separated and combined effects of Bifidobacteria and resveratrol (RSV) against obesity and NAFLD. NAFLD was caused by high-fat diet (HFD) feeding for 8 weeks. HFD-treated mice were orally treated with B. longum (1 × 109 CFU/mouse/day), RSV (100 mg/kg/day), and both of them from the fifth week. HFD feeding caused obesity and NAFLD as indicated by significantly increased body and liver weights, liver steatosis, elevated serum transaminases and lipid profiles, increased inflammation and imbalanced redox status. Based on these physical and biochemical parameters, inflammatory and antioxidant markers, individual administration of B. longum and RSV alleviated obesity and NAFLD, while coadministration of both products further enhanced the efficacy. These data suggested that combined prebiotic RSV and probiotic B. longum would be a potential candidate or adjuvant for the treatment of obesity and NAFLD.

Targeted delivery of emodin to adipocytes by aptamer-functionalized PEG-PLGA nanoparticles in vitro

Targeted delivery of antiobesity drugs to adipocytes presents a novel strategy for obesity treatment. The 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is an attractive therapeutic target of obesity. Emodin (EMO) has been proven to be a potent and selective inhibitor of 11β-HSD1, but it frequently exerts low bioavailability owing to its poor water solubility and lack of tissue specificity. In this work, we conjugated a nanoscale drug delivery polymer with Adipo8 (Ap), a DNA aptamer with high affinity to mature white adipocytes, as a targeting modality that enabled selective delivery of emodin to adipocytes. Emodin-loaded PEG-PLGA nanoparticles (EMO-NPs) were formulated by a modified oil-in-water (O/W) emulsion solvent evaporation method, and Ap was covalently bound to the NP surface via the EDC/NHS method. The NPs were structurally investigated by TEM imaging, DLS and UV-VIS spectroscopy. The resulting aptamer-conjugated, emodin-loaded nanoparticles (Ap-EMO-NPs) had a spherical shape and an average particle size of 146.7 ± 27.85 nm with a drug loading of around 6.8% and a sustained-release property. Confocal microscopy and flow cytometry demonstrated a significant increase in the internalization of Ap-EMO-NP in differentiated 3T3-L1 cells compared to EMO-NP functionalized with nonspecific aptamer. As confirmed by Oil Red O coloring, the Ap-EMO-NPs reduced lipid stacking in 3T3-L1 adipocytes in a sustained-release and dose-dependent manner. The results indicated that Adipo8-functionalized PEG-PLGA NPs could be a potential targeted therapeutic delivery vehicle for obesity treatment.

Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism

The global obesity epidemic has necessitated the search for better intervention strategies including the exploitation of the health benefits of some gut microbiota and their metabolic products. Therefore, we examined the gut microbial composition and mechanisms of interaction with the host in relation to homoeostatic energy metabolism and pathophysiology of dysbiosis-induced metabolic inflammation and obesity. We also discussed the eubiotic, health-promoting effects of probiotics and prebiotics as well as epigenetic modifications associated with gut microbial dysbiosis and risk of obesity. High-fat/carbohydrate diet programmes the gut microbiota to one predominated by Firmicutes (Clostridium), Prevotella and Methanobrevibacter but deficient in beneficial genera/species such as Bacteroides, Bifidobacterium, Lactobacillus and Akkermansia. Altered gut microbiota is associated with decreased expression of SCFA that maintain intestinal epithelial barrier integrity, reduce bacterial translocation and inflammation and increase expression of hunger-suppressing hormones. Reduced amounts of beneficial micro-organisms also inhibit fasting-induced adipocyte factor expression leading to dyslipidaemia. A low-grade chronic inflammation (metabolic endotoxaemia) ensues which culminates in obesity and its co-morbidities. The synergy of high-fat diet and dysbiotic gut microbiota initiates a recipe that epigenetically programmes the host for increased adiposity and poor glycaemic control. Interestingly, these obesogenic mechanistic pathways that are transmittable from one generation to another can be modulated through the administration of probiotics, prebiotics and synbiotics. Though the influence of gut microbiota on the risk of obesity and several intervention strategies have been extensively demonstrated in animal models, application in humans still requires further robust investigation.

Obstructive sleep apnea in obese minipigs.

Objective:Obesity has reached epidemic proportions and is a strong risk factor for obstructive sleep apnea (OSA). However, the underlying mechanisms are poorly understood and current treatment strategies for OSA and obesity have critical limitations. Thus, establishment of an obesity-related large animal model with spontaneous OSA is imperative.Materials and methods:Natural and sedated sleep were monitored and characterized in 4 obese (body mass index - BMI>48) and 3 non-obese (BMI<40) minipigs. These minipigs were instrumented with the BioRadio system under sedation for the wireless recording of respiratory airflow, snoring, abdominal and chest respiratory movements, electroencephalogram, electrooclulogram, electromyogram, and oxygen saturation. After instrumentation, the minipigs were placed in a dark room with a remote night-vision camera for monitoring all behaviors. Wakefulness and different sleep stages were classified, and episodes of apneas and/or hypopneas were identified during natural and/or sedated sleep.Results:No hypopnea episodes were observed in two of the non-obese minipigs, but one non-obese minipig had 5 hypopnea events. Heavy snoring and 27-58 apnea and/or hypopnea episodes were identified in all 4 obese minipigs. Most of these episodes occurred in the rapid eye movement stage during natural sleep and/or sedated sleep in Yucatan minipigs.Conclusions:Obese minipigs can experience naturally occurring OSA, thus are an ideal large animal model for obese-related OSA studies.

Obesity in kidney transplantation

The prevalence of obesity among patients with chronic kidney disease continues to increase as a reflection of the trend observed in the general population. Factors affecting the access to the waiting list and the transplantability of this specific population will be analysed. From observational studies, kidney transplantation in obese patients carries an increased risk of surgical complications compared to the nonobese population; therefore, many centres have been reluctant to proceed with transplantation, despite this treatment modality confers a survival advantage over dialysis. As a consequence, obese patients continue to face decreased access to the waiting list, with a lower likelihood of being transplanted and higher waiting times when compared to the nonobese candidates. In this review will be described the current strategies for treatment of obesity in different settings (pretransplant, at transplant and post-transplant). Obesity represents a risk factor for surgical complications but not a contraindication for kidney transplantation; outcomes could be greatly improved with its multidisciplinary and multimodal treatment. The modern technology with minimally invasive techniques, mainly using robotic platform, allows a reduction in the surgical complications rate, with graft and patient survival rates comparable to the nonobese counterpart.

Notes From the Field: Creating a Typology of Childhood Obesity Intervention Strategies.

Classification systems can be useful for evaluating and communicating the impact of interventions. We describe how a typology was created to inform the development of a community intervention dose index (CIDI) intended to measure the strength of impacts attributed to multiple childhood obesity intervention strategies implemented in a large, diverse urban jurisdiction in the United States during 2000-2016. The categorization system was constructed via a three-stage process: (Stage 1) identify relevant constructs for categorizing intervention strategies; (Stage 2) review peer-reviewed literature and program requests for proposals to identify and integrate common attributes of intervention strategies based on Stage 1 constructs; and (Stage 3) vet the results from prior stages to develop a final version of the typology, slated for research application and for use in program improvement. The final system grouped strategies into four macrolevel and five microlevel categories. Macrolevel strategies included government/public institutional policies, infrastructure investments, and business practices. Microlevel strategies included group education, counseling, health communication and social marketing, home visitation, and screening and referral. Grouping intervention strategies in a purposeful, classified manner facilitated communications among researchers and practitioners during the gathering and quantifying of intervention data for the CIDI project and may be used to guide scarce public health resource allocation decisions.

Healthism and the experiences of social, healthcare and self-stigma of women with higher-weight

This study analyses how the discourse of healthism contributes to the social construction of weight stigma in women with higher-weight. In-depth semi-structured interviews were conducted with nine women who had undergone bariatric surgery and had lived with higher-weight during many years. A thematic analysis from a latent and constructionist perspective showed how the discourse of healthism was behind the experiences of stigma lived by the participants in the social and healthcare field. Even instances of self-stigma were found in our data. This study also illustrates how people influenced by healthism assumed individualism and the importance of body shape, core values of neoliberal consumer societies. In this way, people tended to blame women with higher-weight for their weight and to discriminate against for being far from the socially established ideal body. The findings can be useful to prevent weight stigmatization and to promote more appropriate and respectful strategies for obesity prevention and treatment.

Anti lipase activity of Rosa damascena extracts

OBESITY is a global health concern associated with high morbidity and mortality.One of the strategies in prevention or treatment of obesity is inhibition of pancreatic lipase responsible of absorption of fats. The aim of this study was to evaluate the anti-lipase activity of Rosa damascena Mill. Petal extracts (hydroalcoholic extract, aqueous extract, essential oil and hydrosol). Extracts were assayed for their in vitro activity against PPL (porcine pancreatic lipase) by using spectrophotometry with 2, 4-dinitrophenyl butyrate as substrate. extracts exhibited different anti-lipase activity, alcoholic extract had the highest (62%) anti-lipase activity and is equivalent to 0.11 μg orlistat/mL. followed by essential oil, aqauose extract and rose water with) 55%, 46 and 20% inhibition), respectively. This study supports investigation of effectiveness of these extracts in vivo to be safe and cheap natural medical replacement in the future.

TRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis

tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRFGluTTC, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRFGluTTC also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRFGluTTC directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRFGluTTC suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (aP2, PPARγ, and C/EBPα). In conclusion, these results imply that tRFGluTTC may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity.

An Ancient Chinese Herbal Decoction Containing Angelicae Sinensis Radix, Astragali Radix, Jujuba Fructus, and Zingiberis Rhizoma Recens Stimulates the Browning Conversion of White Adipocyte in Cultured 3T3-L1 Cells.

Background Abnormal storage of white adipocyte tissue (WAT) is the major factor causing obesity. The promising strategies for obesity treatment are building up the brown adipocyte tissue (BAT) and/or expedite fatty acid catabolism. Traditional Chinese Medicine (TCM) sheds light on preventing obesity. Ginger is one of the most effective herbs for antiobesity by accelerating browning WAT. To fortify the antiobesity effect of ginger, an ancient Chinese herbal decoction composed of four herbs, Angelicae Sinensis Radix (ASR), Astragali Radix (AR), Jujuba Fructus (JF), and Zingiberis Rhizoma Recens (ZRR; ginger), was tested here: this herbal formula was written in AD 1155, named as Danggui Buxue Tang (DBT1155). Therefore, the antiobesity function of this ancient herbal decoction was revealed in vitro by cultured 3T3-L1 cells. Materials and Method The lipid accumulation was detected by Oil Red O staining. Furthermore, the underlying working mechanisms of antiobesity functions of DBT1155 were confirmed in 3T3-L1 cells by confocal microscopy, western blot, and RT-PCR. Results DBT1155 was able to actuate brown fat-specific gene activations, which included (i) expression of PPARγ, UCP1, and PCG1α and (ii) fatty acid oxidation genes, i.e., CPT1A and HSL. The increase of browning WAT, triggered by DBT1155, was possibly mediated by a Ca2+-AMPK signaling pathway, because the application of Ca2+ chelator, BAMPTA-AM, reversed the effect. Conclusion These findings suggested that the herbal mixture DBT1155 could potentiate the antiobesity functions of ginger, which might have potential therapeutic implications.

Sa1976 LARGEST EMR AND ESD IN THE WORLD: A NEW METHOD FOR WEIGHT LOSS

Laparoscopic sleeve gastrectomy (LSG) is the most favored surgical bariatric procedure for the treatment of obesity. However, LSG procedure is associated with removal of the greater curvature of the stomach its blood vessels and nerves. Inspired by the complication of esophageal stenosis after endoscopic submucosal dissection (ESD), we hypothesized that resection of a sufficiently large area of the gastric mucosa should result in contracture and a reduction in gastric volume and provide a new strategy for medical treatment of obesity.

Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake

We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean± SE) 31.2± 1.6 years and BMI= 27± 1.5kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2weeks immediately followed by the alternate diet for 2weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508± 106kcal/day; p= 0.0001), with increased consumption of carbohydrate (280± 54kcal/day; p< 0.0001) and fat (230± 53kcal/day; p= 0.0004), but not protein (-2± 12kcal/day; p= 0.85). Weight changes were highly correlated with energy intake (r= 0.8, p< 0.0001), with participants gaining 0.9± 0.3kg (p= 0.009) during the ultra-processed diet and losing 0.9± 0.3kg (p= 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.

Severe Obesity in the Pediatric Population: Current Concepts in Clinical Care.

This review describes (1) the clinical assessment of pediatric patients with severe obesity, including a summary of salient biological, psychological, and social factors that may be contributing to the patient's obesity and (2) the current state of treatment strategies for pediatric severe obesity, including lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Lifestyle modification therapy alone is insufficient for achieving clinically significant BMI reduction for most youth with severe obesity and metabolic and bariatric surgery, though effective and durable, is not a scalable treatment strategy. Pharmacological agents in the pipeline may 1day fill this gap in treatment. Treatment of severe pediatric obesity requires a chronic care management approach utilizing multidisciplinary teams of health care providers and multi-pronged therapies.

Voluntary wheel running reduces weight gain in mice by decreasing high-fat food consumption

We investigated whether wheel running for just 30 min on 5 days each week, an exercise routine based on recommended levels of physical activity for adults, regulates body weight and food intake in mice. Male C57BL/6 mice were divided into groups and given ad libitum access to high-fat food and standard chow or standard chow only. For 30 min on 5 days each week, mice were treated with an in-cage running wheel which was either open to allow voluntary exercise or locked and could not rotate for control. Wheel running reduced weight gain and fat mass among mice fed high-fat food and standard chow, but not mice fed standard chow only. Wheel running decreased high-fat food consumption. Standard chow intake was unchanged. Mice provided with a locked running wheel but pair-fed the same amount of food as wheel running mice also displayed reduced weight gain and fat mass. We conclude that voluntary wheel running for 30 min on 5 days each week reduced weight gain and fat mass in mice by preferentially decreasing high-fat food intake. This model of voluntary wheel running can be used to investigate mechanisms underlying the benefits of exercise on body weight and food intake, informing obesity intervention strategies for humans.