Senescence markers in subcutaneous preadipocytes differ in childhood- versus adult-onset obesity before and after weight loss.

OBJECTIVE: The aim of this study was to determine the effect of age of obesity onset on senescence-related markers in abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) before and after moderate (~10%) weight loss. METHODS: AB and FEM SAT were collected from human females with childhood-onset obesity (CO) or adult-onset obesity (AO) before and after diet- and exercise-induced weight loss. Immunofluorescence analysis of γH2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated ß-galactosidase (SA-ß-gal) activity was measured in SAT. RESULTS: CO had proportionately more AB and FEM preadipocytes with DNA damage (γH2AX+ ) and senescence markers (p53+ and/or p21+ ) than AO at baseline. The proportion of γH2AX+ FEM preadipocytes declined with weight loss in CO and was similar between groups after weight loss. The number of γH2AX foci in γH2AX+ preadipocytes decreased similarly between groups and regions with weight loss in parallel with an increase in RAD51. The proportion of p53+ and p21+ preadipocytes and SA-ß-gal+ cells in SAT did not change with weight loss, but the total p21 intensity in p53+ /p21+ FEM preadipocytes declined in AO. CONCLUSIONS: These results provide preliminary evidence that females with CO have an accelerated preadipocyte aging state that improves with weight loss in terms of DNA damage but not senescence.

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

BACKGROUND: Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. OBJECTIVES: To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. SETTING: University hospital. METHODS: A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. RESULTS: The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). CONCLUSIONS: The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Putting ATM to BED: How Adipose Tissue Macrophages Are Affected by Bariatric Surgery, Exercise, and Dietary Fatty Acids.

With increasing adiposity in obesity, adipose tissue macrophages contribute to adipose tissue malfunction and increased circulating proinflammatory cytokines. The chronic low-grade inflammation that occurs in obesity ultimately gives rise to a state of metainflammation that increases the risk of metabolic disease. To date, only lifestyle and surgical interventions have been shown to be somewhat effective at reversing the negative consequences of obesity and restoring adipose tissue homeostasis. Exercise, dietary interventions, and bariatric surgery result in immunomodulation, and for some individuals their effects are significant with or without weight loss. Robust evidence suggests that these interventions reduce chronic inflammation, in part, by affecting macrophage infiltration and promoting a phenotypic switch from the M1- to M2-like macrophages. The purpose of this review is to discuss the impact of dietary fatty acids, exercise, and bariatric surgery on cellular characteristics affecting adipose tissue macrophage presence and phenotypes in obesity.

Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity.

OBJECTIVE: The inflammatory environment in lower-body subcutaneous adipose tissue (SAT) has been largely unexplored. This study aimed to examine the effects of region (upper body vs. lower body) and sex on SAT immune cell profiles in young adults with obesity. METHODS: Abdominal (AB) and femoral (FEM) SAT was collected from 12 males (mean [SEM] age = 30.8 [1.4] years; mean [SEM] BMI = 34.1 [1.1] kg/m2 ) and 22 females (mean [SEM] age = 30.6 [0.6] years; mean [SEM] BMI = 34.0 [0.7] kg/m2 ) with obesity via needle aspiration. Flow cytometry was used to quantify macrophage (CD68+) and T-cell (CD3+) subpopulations in the stromovascular fraction of each SAT region. RESULTS: Females had a greater proportion of most T-cell types (CD3+CD4+CD45RA+, CD3+CD4+CD45RA-, and CD3+CD8+CD45RA+) in FEM compared with AB SAT, while males had similar proportions in both regions. Regardless of sex, the M1-like macrophage population (CD68+CD206-) was proportionally higher in AB SAT than in FEM SAT. CONCLUSIONS: Results showed that T-cell populations vary by SAT region in females but not males. Both sexes, however, have proportionately more proinflammatory macrophages in upper-body than in lower-body SAT. It remains to be seen how these unique immune cell profiles in males and females with obesity contribute to adipose tissue inflammation and metabolic disease risk.

Meeting fruit and vegetable consumption and physical activity recommendations among adolescents intending to lose weight.

Two-thirds of adolescents who are overweight or have obesity report weight loss intentions. Most report using weight loss strategies consistent with expert recommendations for obesity prevention; however whether they meet recommended fruit and vegetable (F&V) intake and physical activity (PA) recommendations is unknown. We investigated whether weight loss attempts, and weight loss strategies were associated with meeting F&V and PA recommendations. Data were from the 2010 National Youth Physical Activity and Nutrition Study, which surveyed a cross-sectional, nationally representative sample of U.S. high school students. Analyses were restricted to overweight/obese students (n = 2841). Adjusted logistic regression models assessed the odds of meeting daily F&V and weekly PA recommendations after adjusting for grade, sex, race/ethnicity and perceived weight status. Compared to students who were overweight and were not currently intending to lose weight, students who were overweight and intending to lose weight were not more likely to meet F&V or PA. Among students with obesity, those who intended to lose weight were more likely than students who were not currently intending to lose weight to meet F&V recommendations (OR: 3.62, 95% CI: 1.70-7.73). Students who were overweight/obese and used F&V or PA for weight loss were significantly more likely to meet the corresponding recommendation than students intending to lose weight without specific strategies. Weight loss attempts alone do not affect the likelihood of meeting most expert recommendations. Public health efforts emphasizing recommended strategies for healthy eating and active living still need to be encouraged for overweight/obese youth.

Regional adiposity and markers of inflammation in pre-school age children.

In adults, upper body fat partially increases metabolic disease risk through increasing systemic inflammation. Our objective was to determine if this relationship exists in preschool-aged children. A subset of children (n = 71, 35 males), 3.7 ± 1.0 y, were studied from n = 515 children recruited from randomly selected daycares in Montréal, QC. According to WHO charts for 2-5 y, 49 children were healthy weight (HW) and 21 were overweight (OW). Adiposity was determined through dual-energy x-ray absorptiometry. Blood concentrations of C-reactive protein (CRP) and tumour necrosis factor alpha (TNFα) were determined via enzyme-linked immunosorbent and multiplex assays, respectively. OW children had higher (p = 0.03) android:gynoid ratio 0.50 ± 0.09 compared to HW children 0.56 ± 0.12, indicating excess fat was predominantly stored in the abdominal depot. CRP was higher (p = 0.01) in OW children 1.45 ± 2.02 mg/L compared to HW 0.74 ± 1.38 mg/L. Percent fat was correlated with CRP (r = 0.32; p < 0.01) and TNFα (r = 0.25; p = 0.04) concentrations. CRP also correlated with android adiposity (r = 0.24; p = 0.04) and TNFα correlated with gynoid adiposity (r = 0.24; p = 0.04). We observed that greater adiposity is associated with higher systemic inflammation in pre-school aged children. Future longitudinal studies are needed to understand the long term consequences of excess total and regional body fat in young children.

Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs.

Acute Female Hypogonadism Alters Adipose Tissue Fatty Acid Storage Factors and Chylomicronemia.

CONTEXT: Chronic sex steroid deficiency has effects on adipose fatty acid (FA) storage mechanisms and fat oxidation, but the chronology of events are not well understood. OBJECTIVE: The objective of the study was to examine the acute effects of female sex steroid suppression on cellular mechanisms affecting abdominal and femoral subcutaneous adipose tissue FA storage. DESIGN: This study had a randomized, longitudinal, parallel study design. SETTING: The study was conducted at the Mayo Clinic Clinical Research Unit. PARTICIPANTS: Thirty-eight nonsmoking premenopausal women aged 18-50 years participated in the study. INTERVENTION: The intervention included randomization to receive one of the following: 1) no treatment (control), 2) 3.75 mg of Lupron, or 3) 3.75 mg of Lupron and estrogen, but not progesterone, replacement for 49 days, resulting in at least 4 weeks of sex steroid suppression. MAIN OUTCOME MEASURES: Body composition, fat cell size, postprandial chylomicron and nonchylomicron triglyceride concentrations, adipose tissue meal FA storage, direct free fatty acid storage, lipoprotein lipase, acyl CoA synthetase, and diacylglycerol acyltransferase activities, and CD36 content were measured. RESULTS: Compared with the control group, the fed state femoral lipoprotein lipase activity was reduced in women taking Lupron and those taking Lupron and estrogen replacement. In addition, we observed significantly greater postprandial chylomicronemia in the Lupron group than in the other two groups. There were no differences in overall fat storage and oxidation. Depending on the mode of data expression (per unit lipid vs per 1000 adipocytes), there were modest changes in acyl CoA synthetase, diacylglycerol acyltransferase, and CD36 in response to acute sex hormone suppression. CONCLUSIONS: Our results suggest estrogen and progesterone may have different effects on the regulation of FA metabolism and that acute sex steroid deficiency in women does not alter fat storage and oxidation.

Adipocyte fatty acid storage factors enhance subcutaneous fat storage in postmenopausal women.

Increases in weight have been associated with corresponding increases in insulin resistance in postmenopausal women. Although estrogen has significant impact on body fat and body fat distribution, the cellular mechanisms that influence this process are not yet known. We measured adipose tissue fatty acid (FA) storage and FA storage factors in 12 premenopausal and 11 postmenopausal women matched for age and body composition. Postmenopausal women had lower postprandial FA oxidation (indirect calorimetry), greater meal FA, and direct free FA (FFA) storage than premenopausal women, including two-fold greater meal FA storage in the femoral depot. The fed/fasted activities of adipose tissue lipoprotein lipase were not significantly different between premenopausal and postmenopausal women. In contrast, adipocyte acyl-CoA synthetase and diacylglycerol acyltransferase activities in postmenopausal women were significantly upregulated and were positively correlated with direct FFA storage rates. These findings suggest that the propensity for subcutaneous adipose tissue FA storage is increased in postmenopausal women, more so from changes in adipocyte FA storage factors than from adipose tissue lipoprotein lipase activity. Our results suggest that female sex steroids, most likely estrogen, have important effects on adipose tissue FA storage and FA oxidation that could promote fat gain in postmenopausal women.

Effects of male hypogonadism on regional adipose tissue fatty acid storage and lipogenic proteins.

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [(3)H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-(13)C]palmitate and [1-(14)C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans.

Effects of estrogen and testosterone on resting energy expenditure in older men.

The mechanisms by which sex hormones cause changes in body composition are unclear. Sex steroid deficiency might directly reduce energy expenditure/fat oxidation and thereby predispose to increased body fat. Alternatively, sex steroid deficiency could result in lean tissue loss and thus reduced energy expenditure. Our objective was to examine the independent and combined effects of acute testosterone and estrogen withdrawal on respiratory exchange ratio (RER) and resting energy expenditure (REE) in men. The objective of the study was to examine the independent and combined effects of acute estrogen and testosterone withdrawal on RER and REE in men. A total of 54 men aged 50-80 years, BMI range of 17-35 kg/m(2) underwent a 3-week eugonadal run-in hormone-treatment period involving suppression of endogenous sex steroids using letrozole and leuprolide acetate (Lupron) while sex steroid concentrations were maintained with transdermal testosterone (T) and estradiol (E). A second Lupron injection was then given and participants were randomized to one of the following four 3-week treatment groups: group A (-T, -E), group B (-T, +E), group C (+T, -E), and group D (+T, +E). REE and RER were measured via indirect calorimetry before and after the 3-week treatment period. Three-week suppression and/or repletion of estrogen or testosterone did not produce changes in RER or REE within or between groups. We conclude that abrupt changes in sex steroids does not change resting substrate oxidation, indicating that changes that can be observed after more prolonged periods of deficiency are most likely due to direct effects of sex steroids on body composition.

The influence of sex and obesity phenotype on meal fatty acid metabolism before and after weight loss.

BACKGROUND: Regional differences in meal fat storage may explain the preservation of fat accumulation in obese persons. OBJECTIVE: The objective was to determine whether meal fatty acid (FA) metabolism differs by sex and obesity phenotypes before and after weight loss. DESIGN: A [(3)H]triolein-containing meal was given to trace meal FA oxidation ((3)H(2)O generation) and adipose tissue uptake (abdominal subcutaneous and gluteal biopsy samples) in 13 upper-body obese (UOb) men, 9 UOb women, and 8 lower-body obese (LOb) women (study 1). Dual-energy X-ray absorptiometry and abdominal computed tomography were used to measure fat distribution. The subjects participated in a diet and exercise weight-loss program, after which 23 subjects returned for an identical study (study 2). RESULTS: In study 1, the storage of meal FA (mg meal fat/g adipose lipid) was greater in gluteal than in abdominal fat (P = 0.022) in LOb women, but not in UOb women or UOb men. UOb men stored a lesser percentage of meal FAs in both upper- and lower-body subcutaneous fat than did the LOb and UOb women (P = 0.001 and P = 0.044, respectively). The participants who returned for study 2 had lost 14.1 +/- 1.1 kg. Changes in the uptake of meal FAs followed a pattern indicative of obesity phenotype maintenance by group. The uptake of meal FAs increased in upper-body subcutaneous fat (P = 0.028) in weight-reduced UOb women and UOb men (P = 0.046) and decreased in lower-body fat (P = 0.025) in UOb men. CONCLUSION: The differences in meal FA trafficking by obesity phenotype suggest that meal FA storage may play a role in regulating body fat distribution in obese persons.

An investigation of hormone and lipid associations after weight loss in women.

OBJECTIVE: The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss. METHODS: Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels. RESULTS: Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss. CONCLUSION: Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

Probiotics and their potential health claims.

Many studies have attempted to identify specific positive health effects of probiotics. One of the challenges in generalizing health effects of probiotics is that different strains exert disparate effects on human health. As a result, the efficacy of one strain or species cannot necessarily be inferred from another. The objective of this review is to examine the current scientific literature that could be used as the basis for potential health claims. More specifically, this paper will review existing evidence of different probiotic strains to prevent and treat diarrhea, treat irritable bowel syndrome (IBS), treat inflammatory bowel disease, and prevent colon cancer. The strongest evidence is related to the use of Lactobacillus rhamnosus GG in the prevention and treatment of rotavirus-associated diarrhea. Further examination of the literature also shows promise in the treatment of some forms of IBS with probiotics. Future studies that use consistent supplementation regimes will allow more definitive conclusions to be drawn on the effects of probiotics on IBS, inflammatory bowel disease, and colon cancer.