High Fat Diet\u2010Induced Obesity Alters Cutaneous Immune Cell Function, and These Changes Persist After Weight Loss

BackgroundAmong the undesirable changes associated with obesity, one possibility recently raised is dysbiosis of the intestinal microbiota. Studies have shown changes in microbiota in obese rats and humans, but there are still few studies that characterize and compare the fecal microbiota of lean, obese and dogs after weight loss. Thus, this study aimed to evaluate the effects of a weight loss program (WLP) in fecal microbiota of dogs in addition to comparing them with those of lean dogs. Twenty female dogs of different breeds, aged between 1 and 9 years were selected. They were equally divided into two groups: Obese group (OG), with body condition score (BCS) 8 or 9/9, and body fat percentage greater than 30%, determined by the deuterium isotope dilution method, and lean group (LG) with BCS 5/9, and maximum body fat of 15%. Weight loss group (WLG) was composed by OG after loss of 20% of their current body weight. Fecal samples were collected from the three experimental groups. Total DNA was extracted from the feces and these were sequenced by the Illumina methodology. The observed abundances were evaluated using a generalized linear model, considering binomial distribution and using the logit link function in SAS (p < 0.05).ResultsThe WLP modulated the microorganisms of the gastrointestinal tract, so that, WLG and LG had microbial composition with greater biodiversity than OG, and intestinal uniformity of the microbiota (Pielou’s evenness index) was higher in OG than WLG dogs (P = 0.0493) and LG (P = 0.0101). In addition, WLG had values of relative frequency more similar to LG than to OG.ConclusionThe fecal microbiota of the studied groups differs from each other. The weight loss program can help to reverse the changes observed in obese dogs.

BackgroundMaternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects.ResultsFemale mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; −13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized.ConclusionsThis study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0188-3) contains supplementary material, which is available to authorized users.

Overweight is an increasingly prevalent condition throughout the world. Current estimates, which are probably conservative, indicate that at least 500 000 000 people worldwide are overweight as defined by a body mass index (BMI) of between 25.0 and 29.9 and an additional 250 000 000 are obese with a BMI of 30.0 or higher.1 In the United States, recent data indicate that as much as 66% of the adult population is overweight or obese.2 Overweight and obesity are established risk factors for cardiovascular disease (CVD), stroke, noninsulin dependent diabetes (NIDDM), certain cancers, and numerous other disorders.3,4,5,6,7 It is also a risk factor for hypertension.8 Hypertension, defined as a systolic blood pressure in excess of 140 mm Hg or a diastolic blood pressure higher than 90 mm Hg, is also a globally increasing public health concern. Roughly 1 billion individuals worldwide are estimated to exhibit clinically significant elevated blood pressure with about 50 million of those residing in the United States.8 Hypertension, in turn, is associated with increased risk for CVD, stroke, renal disease, and all-cause mortality.9,10,11,12 The JNC VII report defines Stage 1 hypertension as blood pressure levels between 140 and 159 mm Hg systolic and 90 and 99 diastolic. Additionally, the report establishes a category of Prehypertension (Systolic blood pressure between 120 and 140 mm Hg or diastolic between 80 and 89 mm Hg). These 2 blood pressure classifications are deemed to be appropriate primary targets for lifestyle modification interventions, including weight loss. Higher levels of blood pressure, or stage 1 hypertension that is maintained over a long period, should be addressed primarily with medications or other physician directed treatments. There is a positive relationship between overweight or obesity and blood pressure and risk for hypertension. As early as the 1920s, a significant …

Heart rate variability in obesity and the effect of weight loss

To investigate the extent of carotid artery atherosclerosis in obese subjects and to examine the possible effects of weight loss on atherosclerotic development. Controlled 4 y intervention study. 20 obese patients treated with weight-reducing gastroplasty, 19 obese patients treated with dietary recommendations and 35 lean subjects. Body weight, blood pressure, blood lipids, glucose and insulin were measured. A B-mode ultrasound was recorded to determine the intima-media thickness (IMT) and lumen diameter (LD) of the carotid artery. Study groups were investigated at baseline and re-examined after 3 to 4 y of follow-up. At baseline, obese patients had higher blood pressure, serum total cholesterol, triglycerides, glucose and insulin compared with lean subjects; they also had a larger IMT in the carotid artery bulb (P<0.05) and a larger LD in the common carotid artery (P<0.01). After 4 y of follow-up, obese patients treated with surgery displayed a mean weight loss of 22 kg (19%), while the average weight in the obese control group remained unchanged (P<0.001). The weight loss group showed improvements in blood pressure, HDL-cholesterol, triglycerides and insulin compared with the obese control group (P<0.05). The progression rate of carotid bulb IMT in the weight loss group was similar to that observed in the lean control group (0.024 vs 0.025 mm/y, n.s.), whereas the IMT progression rate was almost three times higher in the obese control group (0.068 mm/y, P<0.05 compared with lean controls). Obese people have an unfavourable risk factor profile and signs of premature carotid artery atherosclerosis. Weight loss is followed by an improvement in several risk factors and may reduce the progression rate of atherosclerotic changes in the carotid artery bulb.

Influence of Obstructive Sleep Apnea on Endothelial Function in Obese Patients: Response

To provide a firmer basis for preventing high blood pressure (BP), we tested interventions to promote weight loss, dietary sodium reduction, and their combination for lowering diastolic BP, systolic BP, and the incidence of hypertension during a 3- to 4-year period. We conducted a randomized, 2 x 2 factorial, clinical trial, with BP levels measured by blinded observers. Nine academic medical centers recruited 2382 men and women (age range, 30-54 years) not taking antihypertensive drugs, with a diastolic BP of 83 to 89 mm Hg, a systolic BP lower than 140 mm Hg, and a body mass index (the weight in kilograms divided by the square of the height in meters) representing 110% to 165% of desirable body weight. Counseling aimed at helping participants achieve their desirable weight or a 4.5-kg or more weight reduction (in the weight loss and combined groups) and/or sodium intake of 80 mmol/d (in the sodium reduction and combined groups) was provided. From baseline, participants' weight decreased by 4.3 to 4.5 kg at 6 months and by approximately 2 kg at 36 months in the weight loss and combined groups compared with weight changes in the usual care group (all groups, P < .001). Sodium excretion decreased 50 and 40 mmol/d at 6 and 36 months, respectively, in the sodium reduction group and about 15 mmol/d less at each time point in the combined group compared with the usual care group (all groups, P < .01). Compared with the usual care group, BP decreased 3.7/2.7 mm Hg in the weight loss group, 2.9/1.6 mm Hg in the sodium reduction group, and 4.0/2.8 mm Hg in the combined group at 6 months (all groups, P < .001). At 36 months, BP decreases remained greater in the active intervention groups than in the usual care group (weight loss group, 1.3/0.9 mm Hg; sodium reduction group, 1.2/0.7 mm Hg; combined group, 1.1/0.6 mm Hg). Differences were statistically significant for systolic and diastolic BP in the weight loss group and for systolic BP in the sodium reduction group. Through 48 months, the incidence of hypertension (BP > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic or the use of antihypertensive drugs) was significantly less in each active intervention group than the usual care group (average relative risks, 0.78-0.82). In overweight adults with high-normal BP, weight loss and reduction in sodium intake, individually and in combination, were effective in lowering systolic and diastolic BP, especially in the short-term (6 months). Although the effects on average BP declined over time, reductions in hypertension incidence were achieved.

Objective: Current evidence suggests that obesity is associated with alteration of sweet taste perception. The purpose of this study was to determine if nonsurgical cognitive behavioral therapy (CBT)-based weight loss can cause a change in sweet taste perception. Methods: This case-control study consisted of 51 women aged 21–64 years. Twenty-seven with obesity or overweight were assigned to an obesity (OB) group (BMI: 29.8 ± 0.5 kg/m²) and 24 to a normal control (NC) group (BMI: 20.9 ± 0.3 kg/m²). The OB group underwent a 30-week weight loss intervention using CBT-based group therapy. The results of measurement of detection threshold, suprathreshold perceived intensity, preference, and palatability, elements of sweet taste perception, were compared before and after the intervention. Psychological variables and appetite-related hormonal levels were measured. Results: Twenty-three patients and 22 controls completed the study. The OB group showed a 14.6% weight loss after the intervention. At baseline, the OB group preferred significantly higher sucrose concentrations than did the NC group; however, this difference was no longer significant after intervention. In the OB group, persistent pleasure and reduced desire for other taste, measured by repeated exposure to sweetness, normalized after weight loss to levels comparable to those seen in the NC group. No significant difference in discriminative perception of the threshold concentration or the suprathreshold sensory value was found between the two groups before or after intervention. A significant correlation was found between the basal preferred sucrose concentration and the serum leptin level of the OB group after adjusting for confounding factors, such as BMI, depressive symptom score, and trait-anxiety scores. Conclusions: Weight loss induced by CBT-based nonsurgical intervention resulted in the normalization of the sucrose preference and palatability of women with obesity. Leptin activity may be associated with the altered sweet taste preference of people with obesity.

The effect of modifying dietary protein and carbohydrate in weight loss on arterial compliance and postprandial lipidemia in overweight women with polycystic ovary syndrome

The independent and combined effects of weight loss and aerobic exercise on blood pressure and oral glucose tolerance in older men

Daily intake of bisphenol A and triclosan and their association with anthropometric data, thyroid hormones and weight loss in overweight and obese individuals

Obesity in the United States is associated with overconsumption of the high fat and high carbohydrate western diet. It is a major risk factor for hypertension. The mechanisms by which obesity contributes to the development of hypertension remain unresolved. While obese women are three-fold more likely to develop hypertension than lean women, the majority of obesity-induced hypertension research has been conducted using male cohorts. Thus, there is an urgent need to investigate the pathophysiology of obesity-induced hypertension in women. A previous study from our lab demonstrated that endothelial dysfunction found in obese female rats is associated with TLR4 signaling activation in the aorta revealing an inflammatory state in a conduit artery during obesity. The goal of this present study is to investigate whether weight loss by reversal of western diet-induced obesity normalizes TLR4 signaling in conduit and resistance arteries. To address this question, eight-week-old female Wistar rats were randomized into three experimental groups: the Obese group (n=10) was fed a western diet (21% fat, 50% carbohydrate [34% sucrose], 20% protein) and the Lean group (n=10) was fed a standard chow diet (5% fat, 48.7% carbohydrate [3.2% sucrose], 24.1% protein) for 20 weeks. The weight loss group (n=10) was fed a western diet for 20 weeks and a standard chow diet for 8 weeks. While weight loss reduced BMI (0.65 ±0.03 vs.0.82 ±0.02 obese, p&lt;0.01), systolic blood pressure consistently measured at 7pm by tail-cuff plethysmography remained elevated (139.83 ± 15.3 vs.150.06 ± 4.5, p=0.09). At the experimental endpoint, thoracic aortas and mesenteric arteries were obtained for molecular analysis of TLR4 signaling. As previously shown, aortic TLR4 signaling of the obese group was activated. Weight loss normalized TLR4 and MyD88 expression in thoracic aortas; however, expression of MyD88 remained increased in mesenteric arteries (2.8 fold increase, p&lt;0.01, n=6). This suggests that persistent hypertension despite weight loss is associated with a failure of TLR4-MyD88 signaling to normalize in the resistance vessels.

Background: Hyperuricemia (hyperUA) is a cardiovascular risk and UA levels might predict future hypertension. In this study, we evaluated the effects of chronic weight loss (WL) on UA levels, renal and cardiac functions. Methods: Obese, mild hypertensive men (n=154) on no medications were measured BMI, total body fat-mass, blood pressures (BP), UA, serum creatinine (Crn), creatinine clearance (CCr), plasma norepinephrine (NE), glucose, insulin (INS), HOMA-IR and ECG before and every 6 month after 2 yrs with WL regimens achieved with mild calorie restriction and exercise. Significant WL was defined as ≥10% WL of entry BMI at 2 yrs. LVH determined by ECG was used as an index or cardiac function parameter. Results: Significant WL (≥10%) were observed 47.8% at 1 yr and 61.8% at 2 yrs, and hyperUA were 64.3% at baseline, 43.3% at 1 yr, and 29.9% at 2 yrs. UA levels, LVH parameters, plasma NE, BMI, fat-mass, and BP levels at entry were greater and CCr was smaller in the non-WL group (&lt;10%) at 2 yrs compared to the WL group, whereas HOMA at entry and changes in HOMA-IR over 2 yrs were similar between WL and non-WL groups. UA, Crn, NE, HOMA, BMI, fat-mass, BP significantly decreased with WL in all subjects, but the decreases in those parameters were greater in the WL group compared to non-WL group. All parameters except CCr at entry were greater in subjects with hyper UA at 2 yrs than those with normal UA at 2 yrs. Changes in NE, HOMA, Crn, CCr, and LVH parameters over 2 yrs in subjects with normal UA at 2 yrs were greater than those with hyper UA at 2 yrs. Changes in UA over 2 yrs significantly correlated with changes in NE, BMI, systolic BP, and fasting glucose (all, P&lt;0.05). UA levels at entry correlated with changes in BMI, changes in CCr and changes in LVH parameters (all, P&lt;0.05). Conclusions: These results demonstrate that chronic WL over 2 yrs is effective to decrease UA levels in obese subjects. Reducing UA levels by WL might link to improving glucose metabolisms, renal function (observed in CCr) and cardiac function (measured by LVH parameters). UA levels could predict the effects of WL on renal and cardiac functions. Suppression of sympathetic nervous activation by WL, but not insulin resistance, might be related to UA reduction associated with WL.

Objective: Obesity and overweight are defined as the excessive accumulation of fat in the body, which generally occurs when energy intake exceeds energy expenditure. Currently, obesity is considered one of the largest public health challenges worldwide and is inversely associated with various health outcomes. Obesity is often linked to inflammatory factors. The purpose of this study was to compare the effects of rapid, moderate, and slow weight loss combined with a low-calorie diet and physical activity on inflammatory markers in obese women. Methods and Materials: In this study, 36 obese women (ages 20 to 45 years) with a body mass index (BMI) of 30 or higher were randomly divided into three groups: rapid weight loss (combined training with 30-35% caloric deficit, 12 weeks, 12 participants), moderate weight loss (combined training with 20-25% caloric deficit, 10 weeks, 12 participants), and slow weight loss (combined training with 15-20% caloric deficit, 15 weeks, 12 participants). Participants underwent interventions for rapid, moderate, or slow weight loss, which included exercise and nutritional programs. Aerobic exercise consisted of walking and jogging on a treadmill at an intensity of 50-65% of maximum heart rate, and resistance training at 40% of one-repetition maximum (1RM), including dumbbell cross movements, biceps curls, and triceps extensions. Inflammatory markers, including Interleukin-1 (IL-1) and high-sensitivity C-reactive protein (hs-CRP), were measured at the beginning and end of the study. Data analysis was performed using ANOVA, Shapiro-Wilk, Levene's test, and covariance analysis. Statistical analyses were conducted using SPSS version 23 at a significance level of 0.05. Findings: Rapid, moderate, and slow weight loss combined with a low-calorie diet and physical activity did not have a significant effect on plasma IL-1 levels in obese women. However, significant differences were observed between the rapid weight loss group and the moderate and slow weight loss groups. Specifically, a 22.66% reduction in IL-1 levels was noted in the moderate weight loss group compared to the rapid weight loss group, and a 39.59% reduction was observed in the slow weight loss group compared to the rapid weight loss group. No significant difference was found between the moderate and slow weight loss groups. Similarly, rapid, moderate, and slow weight loss combined with a low-calorie diet and physical activity did not significantly affect plasma hs-CRP levels in obese women. However, a significant difference was observed between the rapid weight loss group and the slow weight loss group, with a 62.28% reduction in hs-CRP levels in the slow weight loss group compared to the rapid weight loss group. No significant differences were found between the other groups. Conclusion: Rapid, moderate, and slow weight loss combined with a low-calorie diet and physical activity does not significantly impact inflammatory factors.

BackgroundObesity is a leading risk factor for osteoarthritis (OA). In contrast, calorie restriction (CR) may lessen OA due to improved systemic inflammatory status and reduced weight-bearing. The aim of this study was to determine how CR with regular chow versus a high-fat diet (HFD) alters OA progression using the Hartley guinea pig model of disease.MethodsTwenty-four male guinea pigs were allocated to four groups at 2 months of age: (1) ad libitum regular chow (obese), (2) CR regular chow (lean), (3) ad libitum HFD, and (4) CR HFD. Animals in both HFD groups ate identical amounts and were combined into one HFD group for analyses. At 5 months, hind limbs were harvested for microcomputed tomography (microCT) and histopathologic evaluation of knee OA. Total body, gonad fat, and infrapatellar fat pad (IFP) masses were recorded. IFPs were collected for gene expression analysis. Immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1) was performed on intact joints. Serum was utilized for protein C3 measurement. All data were compared using ordinary one-way ANOVA analyses with Tukey’s post-hoc tests.ResultsBody mass in the lean and HFD groups were similar and lower than the obese group. Despite this, gonad fat pads in the HFD group were comparable to the obese group. MicroCT and histologic OA scores were similar in obese and HFD groups; both scores were significantly lower in the lean group. Obese and HFD groups displayed increased gene expression of pro-inflammatory and catabolic mediators in IFPs relative to lean animals. Consistent with this, immunohistochemistry for MCP-1 in knee joints demonstrated strong positive staining in obese and HFD groups but was minimally detected in lean animals. Serum protein C3 levels were also statistically higher.ConclusionsThis study demonstrated that CR with a regular chow diet lessened knee OA in the Hartley guinea pig and was associated with decreased local and systemic inflammation compared to obese animals. HFD animals, although under CR conditions, had OA scores and inflammatory markers similar to obese animals. Thus, diet composition, and not solely body weight, may be a key factor in development of OA.