Objectively Measured Physical Activity Is Lower in Individuals with Normal Weight Obesity in the United States.

The role of physical activity in normal weight obesity (NWO), which is associated with increased cardiometabolic risk, is not clear. This study aimed to determine body composition phenotype-specific differences in objectively measured physical activity and sedentary time in adults in the United States. A total of 2055 adults with a body mass index (BMI) ≥ 18.5 m2 were studied using 2003-2006 National Health and Nutrition Examination Surveys. Physical activity and percent body fat (BF%) were measured using accelerometer and dual-energy X-ray absorptiometry, respectively. A BF% > 23.1% and >33.3% for men and women, respectively, was considered excess. A BMI of 18.5-24.9 kg/m2 with excess BF% was defined as NWO, while those with normal BF%, as normal weight lean (NWL). A BMI of ≥25 kg/m2 with excess BF% was considered overweight/obesity (OB). Compared to NWL, moderate to vigorous physical activity was significantly lower by 8.3 min (95% confidence interval/CI = -15.20, -1.40) and 10.18 min (95% CI = -14.83, -5.54) per day in NWO and OB, respectively. Low-intensity physical activity was also significantly lower by 17.71 min (95% CI = -30.61, -4.81) per day in NWO compared to NWL. However, sedentary time was not different. Objectively measured physical activity is significantly lower in NWO compared to NWL, while sedentary time is not.

Normal weight obesity and unaddressed cardiometabolic health risk-a narrative review.

Normal weight obesity (NWO) is defined as having a normal body mass index (BMI), but a high body fat mass. There is growing interest in individuals with NWO, which is an underdiagnosed and understudied group, because of their increased risk for cardiometabolic morbidity and mortality. In this review, we summarized the definition, prevalence, etiology, pathophysiology, and cardiovascular outcomes seen in NWO. We have also summarized the available literature on interventions for NWO. There is a wide variation in the body fat percent cutoffs used to diagnose excess body fat. Hence, the prevalence rates of NWO vary between different populations and studies. It is estimated that about 30 million Americans have NWO and the worldwide prevalence ranges from 4.5% to 22%. Genetics, diet, and physical activity are related to NWO. However, etiological factors are not clear. Changes in body composition, inflammation, oxidative stress are present in NWO in comparison to normal weight lean (NWL) who have a normal BMI and normal body fat amount. Furthermore, cardiometabolic changes are observed and some are subclinical. Thus, screening for NWO will enhance the primary prevention of cardiovascular disease. Due to the use of various body fat percent cutoffs and methods to measure body fat, it is challenging to compare between studies. Researchers working in this field should ideally work towards developing standard body fat percent cutoffs for diagnosing NWO. There are many gaps in the literature on NWO unlike for overt obesity and future studies should explore the etiology, molecular mechanisms, and adipose tissue changes of NWO as well as conduct well planned and executed randomized controlled trials testing dietary, physical, and behavioral interventions for NWO in both males and females of different racial and age groups.

A short, attribution theory-based video intervention does not reduce weight bias in a nationally representative sample of registered dietitians: a randomized trial.

BACKGROUND/OBJECTIVES: Weight bias among registered dietitians (RDs) is a concern and effective interventions to reduce weight bias are sparse. Our objective was to determine if a short, attribution theory-based online video intervention would reduce weight bias in RDs. SUBJECTS/METHODS: Dietitians from a nationally representative sample were recruited for a randomized, parallel-arm study with online surveys at pre-, post-intervention and 1-month follow-up. One hundred and forty-seven RDs who watched one of three videos embedded in an online survey from June to August 2019 were considered for the analysis. RDs were randomized to watch either the intervention, positive control, or negative control video. The primary outcome was the change in the "blame" component of the Anti-Fat Attitude Test (AFAT) from pre-to immediate post-intervention. Differences in changes in AFAT and Implicit Association Test (IAT) scores across treatment groups were assessed via linear models; multiple imputation were performed for missing data. RESULTS: Baseline demographics, AFAT and IAT scores of the 147 participants who watched a video were not significantly different between the study groups (p > 0.05). The intervention group's AFAT-blame score reduced by an average of 0.05 between pre- and immediate post-intervention but was not statistically significant (p = 0.76, confidence intervals (CI) = -0.40, 0.30). Furthermore, there were no significant changes for AFAT-social, AFAT-physical subscores, and IAT within or between groups between pre- and immediate post-intervention (p > 0.05). Due to high attrition rates, the changes at 1-month follow-up are not reported. CONCLUSIONS: This study was the first to explore the effectiveness of an online video intervention to reduce weight bias in RDs. This study was unable to detect a significant impact of a short, attribution theory-based video intervention on weight bias in practicing RDs and future larger studies are needed to confirm our findings.

Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice.

This study aims to investigate the global profiling of genes and miRNAs expression to explore the regulatory effects of eicosapentaenoic acid (EPA) in visceral adipose tissue (VAT) of obese mice. We used male mice, fed either a high-fat diet (HF) or HF supplemented with EPA (HF-EPA), for 11 weeks. RNA, and small RNA profiling, were performed by RNAseq analysis. We conducted analyses using Ingenuity Pathway Analysis software (IPA®) and validated candidate genes and miRNAs related to lipid mediators and inflammatory pathways using qRT-PCR. We identified 153 genes differentially downregulated, and 62 microRNAs differentially expressed in VAT from HF-EPA compared to HF. Genes with a positive association with inflammation, chemotaxis, insulin resistance, and inflammatory cell death, such as Irf5, Alox5ap, Tlrs, Cd84, Ccr5, Ccl9, and Casp1, were downregulated by EPA. Moreover, EPA significantly reduced LTB4 levels, a lipid mediator with a central role in inflammation and insulin resistance in obesity. The pathways and mRNA/microRNA interactions identified in our study corroborated with data validated for inflammatory genes and miRNAs. Together, our results identified key VAT inflammatory targets and pathways, which are regulated by EPA. These targets merit further investigation to better understand the protective mechanisms of EPA in obesity-associated inflammation.

A randomized cross-over trial to determine the effect of a protein vs. carbohydrate preload on energy balance in ad libitum settings.

BACKGROUND: Although high protein diets have been tested in controlled environments for applications to weight management, it is not understood if adding high protein foods to the diet would impact ad libitum energy balance in the absence of other lifestyle changes. METHODS: This double-blinded randomized crossover trial compared the effects of a protein shake (PS) to a carbohydrate shake (CS), consumed prior to each major meal to equate to 20% of total energy needs over the course of the day, on energy balance over two 5-day treatment periods in healthy adults with BMI 20-30 kg/m2. Tri-axial accelerometers estimated physical activity energy expenditure. Ad libitum energy intake was measured in a laboratory kitchen. RESULTS: Energy balance was positive during both treatment periods but was not different between periods. There were no interactions between treatment and preload caloric dose or treatment and BMI status on energy balance. Satiety ratings did not differ for any pairwise comparisons between treatment and caloric dose. Controlling for gender and basal metabolic rate, thermic effect of food was greater for PS than CS. CONCLUSIONS: Preload periods significantly altered the macronutrient composition of the overall diet. This study found limited evidence that carbohydrate or protein preloads have differential effects on energy balance in short-term ad libitum settings. TRIAL REGISTRATION: This trial was pre-registered on clinicaltrials.gov as NCT02613065 on 11/30/2015.

The effects of a teaching intervention on weight bias among kinesiology undergraduate students.

OBJECTIVES: Weight bias is present among kinesiology professionals and this may cause a significant negative impact on their clients with obesity. Thus, our objective was to test if learning about uncontrollable cause of obesity and about weight bias would reduce explicit and implicit weight bias among kinesiology undergraduate students compared to the traditional curriculum which is more focused on controllable causes of weight gain. METHODS: We recruited undergraduates from two classes of the same kinesiology major course taught by the same instructor. In-class teaching activities consisted of 80 min lecture on day 1, video watching session and a group activity on day 3 for both groups. Intervention group (n = 33) learned about uncontrollable causes of obesity and about weight bias and had activities to evoke empathy. Control group (n = 34) learned the traditional curriculum where they learned the role of exercise and diet in weight management. We measured explicit and implicit weight bias using Anti-Fat Attitude Test (AFAT) and Implicit Association Test (IAT), respectively pre-intervention, immediate post intervention and 1 month later. RESULTS: In mixed model analysis, AFAT Blame scores had significant group by time interaction (p < 0.001). Blame scores significantly reduced with mean differences (standard error (SE)) of -0.35 (0.08) post intervention (p < 0.001) and persisted to be reduced with mean differences (SE) of -0.39 (0.08) even after 4-week follow-up (p < 0.001) only in the intervention group. Odds of having less implicit weight bias was significantly lower at 4-week follow-up than pre-intervention (odds ratio = 0.4; 95% CI: 0.22-0.73) in the control group but no changes were seen in the intervention group. CONCLUSIONS: "Blame" component of explicit weight bias significantly decreased when students learned about controllable causes of obesity and weight bias, but implicit bias did not reduce. However, implicit weight bias appears to increase when education on obesity is limited to diet and exercise interventions as taught in the traditional curriculum.

Subjective social status is associated with compensation for large meals - A prospective pilot study.

OBJECTIVES: Subjective social status (SSS) is known to be inversely associated with obesity. Our objective was to determine if SSS is associated with eating behaviors that would predispose to weight gain, specifically, with inadequate compensation for excess energy consumed during a single large meal. Therefore, we conducted a pilot study to determine the association of SSS with 24-h energy balance, 24-h and post-lunch energy intake, changes in body composition and changes in adjusted resting energy expenditure on days when a high-energy lunch was consumed in free-living human subjects. METHOD: Female participants (7 normal weight and 10 overweight) consumed 60% of' estimated 24-h energy requirements as a lunchtime meal in the laboratory for 14 days. Subjective social status was measured at baseline using the MacArthur Scale. Remote Food Photography Method was used to record food intake outside of the lab on days 1-2, 7-8, and 12-13. Associations of 24-h energy balance, 24-h and post-lunch energy intake, changes in adjusted resting energy expenditure and changes in percent body fat (measured by dual x-ray absorptiometry) with SSS were studied. RESULTS: Mean (standard deviation) age and BMI were 36.29 (8.25) years and 26.43 (2.32) kg/m2, respectively. Lower SSS was significantly associated with positive energy balance (p for trend 0.002), and higher post-lunch energy intake (p = 0.02) when controlled for age and initial body mass index. CONCLUSIONS: Our pilot data show that lower SSS is associated with higher post-lunch energy intake, which is indicative of poor energy compensation following a large meal. Over a longer time period, this could result in fat mass gain. Studies that are of longer duration and well-powered are warranted to confirm our findings.

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice.

Brown adipose tissue (BAT) dissipates chemical energy as heat via thermogenesis and protects against obesity by increasing energy expenditure. However, regulation of BAT by dietary factors remains largely unexplored at the mechanistic level. We investigated the effect of eicosapentaenoic acid (EPA) on BAT metabolism. Male C57BL/6J (B6) mice were fed either a high-fat diet (HF, 45% kcal fat) or HF diet supplemented with EPA (HF-EPA, 6.75% kcal EPA) for 11 weeks. RNA sequencing (RNA-Seq) and microRNA (miRNA) profiling were performed on RNA from BAT using Illumina HiSeq and Illumina Genome Analyzer NextSeq, respectively. We conducted pathway analyses using ingenuity pathway analysis software (IPA®) and validated some genes and miRNAs using qPCR. We identified 479 genes that were differentially expressed (2-fold change, n = 3, P ≤ 0.05) in BAT from HF compared to HF-EPA. Genes negatively correlated with thermogenesis such as hypoxia inducible factor 1 alpha subunit inhibitor (Hif1an), were downregulated by EPA. Pathways related to thermogenesis such as peroxisome proliferator-activated receptor (PPAR) were upregulated by EPA while pathways associated with obesity and inflammation such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated by EPA. MiRNA profiling identified nine and six miRNAs that were upregulated and downregulated by EPA, respectively (log2 fold change > 1.25, n = 3, P ≤ 0.05). Key regulatory miRNAs which were involved in thermogenesis, such as miR-455-3p and miR-129-5p were validated using qPCR. In conclusion, the depth of transcriptomic and miRNA profiling revealed novel mRNA-miRNA interaction networks in BAT which are involved in thermogenesis, and regulated by EPA.

Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity.

AIM: Bariatric surgery induces significant weight loss, increases insulin sensitivity, and reduces mortality, but the underlying mechanisms are not clear. It was hypothesized that Roux-en-Y gastric bypass (RYGB) surgery improves metabolic profile along with weight loss. The objective of this pilot study was to evaluate changes in serum metabolites and fatty acids (FA) at 2 weeks and 6 months after RYGB. MATERIALS AND METHODS: Serum samples were collected pre-surgery, at 2 weeks and 6 months post-surgery from 20 patients undergoing RYGB surgery. Serum non-esterified free FA (NEFA) were measured. Serum metabolites and FA were measured using nuclear magnetic resonance spectroscopy and improved direct fatty acid methyl ester synthesis and the gas chromatography/mass spectrometry method, respectively, in subjects who completed follow-up at 6 months (n = 8). RESULTS: Mean (standard deviation) percent total weight loss was 6.70% (1.7) and 24.91% (6.63) at 2 weeks (n = 15) and 6 months (n = 8) post-surgery, respectively. NEFA were significantly reduced at 6 months post-surgery (P = 0.001, n = 8). Serum branched chain amino acids, 2-aminobutyrate, butyrate, 2-hydroxybutyrate, 3-hydroxybutyrate, acetone, 2-methylglutarate, and 2-oxoisocaproate were significantly reduced, while serum alanine, glycine, pyruvate, and taurine were significantly elevated at 6 months post-surgery compared with pre-surgery (n = 8, P < 0.05). Also, serum FA C10:0, C13:0, C14:0, C15:0, and C18:0 increased significantly (n = 8, P < 0.05) by 6 months post-surgery. CONCLUSIONS: Changes in serum metabolites and FA at 6 months post-RYGB surgery in this pilot study with limited number of participants are suggestive of metabolic improvement; larger studies are warranted for confirmation.

An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

Effect of bariatric surgery on systemic and adipose tissue inflammation.

BACKGROUND: Obese patients are predisposed to developing insulin resistance and associated metabolic diseases such as diabetes and cardiovascular disease. The objective of this study was to determine the effect of bariatric surgery on adipose-derived inflammatory cytokines (adipokines), which play a key role in insulin resistance and obesity. We hypothesized that there is a significant increase in serum and tissue anti-inflammatory adiponectin with a decrease in circulating pro-inflammatory TNF-α and MCP-1, leading to reduced inflammation post-bariatric surgery. METHODS: In this study, we investigated the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic gastric band on serum and tissue levels of adiponectin and serum levels of MCP-1 and TNF-α. Samples of serum and adipose tissue were collected at the time of surgery, 2 weeks and 6 months postoperatively. Adipokine levels were assayed by ELISA kits. RESULTS: A significant increase in adiponectin levels 2 weeks after surgery was observed in the subcutaneous adipose tissue in both groups combined. Serum adiponectin in LRYGB patients showed an increasing trend, while MCP-1 showed a decreasing trend post-surgery. There was no difference in TNF-α among the groups. The number of patients enrolled did not allow for statistical power to be reached. CONCLUSION: Our results show significant and rapid increases in subcutaneous adipose adiponectin as early as 2 weeks post-bariatric surgery demonstrating reduced inflammation and possibly reduced insulin resistance. Future studies are warranted in larger cohorts with additional measurements of insulin sensitivity and inflammation.