Adiposity-related Diseases Research Articles

Association of Adiposity Phenotypes with 27-Hydroxycholesterol and Sex Hormones: The Multiethnic Cohort Study.

The distribution of body fat has been linked to circulating levels of lipids and sex-steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC and steroid hormones with adiposity phenotypes. To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal females. A cross-sectional study was conducted among 912 postmenopausal females from the Multiethnic Cohort- Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone-binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid lowering drugs. Subgroup analyses were conducted across race and ethnicity. Total fat mass (P-trend=0.003), subcutaneous adipose tissue (SAT) (P-trend=0.006), and superficial subcutaneous adipose tissue (sSAT) (P-trend=4.41x10-4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P-trend=0.003) and liver fat (P-trend=0.005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol, testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity. Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal females. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.

Phenotyping of Obesity Treatment Candidates: A Narrative Review.

This review explores characterizing candidates for obesity treatments including pharmacotherapy, endoscopic bariatric therapies, and metabolic bariatric surgery (MBS), focusing on established clinical parameters for diagnosing obesity beyond body mass index alone. Existing literature primarily provides rates for fat mass percentage (i.e., a marker for adiposity quantity), waist circumference (i.e., a marker for adiposity distribution), and C-reactive protein levels (i.e., a marker for adiposity functionality) among obesity treatment candidates. Limited data on abnormal values and sex-based differentiation exist. The literature indicates high central-tendency measures for fat mass percentage and waist circumference, while C-reactive protein levels vary. Data on the Edmonton Obesity Staging System (i.e., a marker for adiposity-related disease severity) is predominantly available for MBS candidates. Future studies in obesity interventions should improve screening and diagnosis of obesity by incorporating sex-specific considerations and providing abnormal value rates for measurements to enhance understanding of patients' characteristics.

Agreement Between Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry to Estimate Fat Mass in Hispanic Adults With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Adipose tissue excess is associated with adverse health outcomes, including type 2 diabetes. Body mass index (BMI) is used to evaluate obesity but is inaccurate as it does not account for muscle mass, bone density, and fat distribution. Accurate measurement of adipose tissue through dual-energy X-ray absorptiometry (DXA) and computed axial tomography (CT) is crucial for managing and monitoring adiposity-related diseases. Still, these are not easily accessible in most hospitals in Mexico. Bioelectrical impedance analysis (BIA) is non-invasive and low-cost but may not be reliable in conditions affecting the body's hydration status, like diabetes. To assess fat mass concordance between BIA and DXA in Hispanic-American adults with type 2 diabetes mellitus (T2DM). Cross-sectional study of a non-probabilistic sample of subjects over 18 years with type 2 diabetes. We used DXA as the reference method. We evaluated the accuracy of FM estimation through BIA and DXA in 309 subjects with type 2 diabetes. Results showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index (FMI). At the group level, we found BIA accurate; however, at the individual level, it is not. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA (P ⩽ .01) in both sexes. BIA demonstrated high precision in estimating fat mass. We were able to provide a correction factor of 0.55 kg in men. BIA is inaccurate compared to DXA for body composition assessment in patients with diabetes. Inaccurate measurements can result in misclassification. However, BIA is precise for body composition assessment in patients with diabetes, so it is reliable for tracking patient progress over time.

Genomics and phenomics of body mass index reveals a complex disease network

Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.

Oenothein B in Eucalyptus Leaf Extract Suppresses Fructose Absorption in Caco-2 Cells.

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 μg/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism.

Glucocorticoids (GCs) are hormones that aid the body under stress by regulating glucose and free fatty acids. GCs maintain energy homeostasis in multiple tissues, including those in the liver and skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT). WAT stores energy as triglycerides, while BAT uses fatty acids for heat generation. The multiple genomic and non-genomic pathways in GC signaling vary with exposure duration, location (adipose tissue depot), and species. Genomic effects occur directly through the cytosolic GC receptor (GR), regulating the expression of proteins related to lipid metabolism, such as ATGL and HSL. Non-genomic effects act through mechanisms often independent of the cytosolic GR and happen shortly after GC exposure. Studying the effects of GCs on adipose tissue breakdown and generation (lipolysis and adipogenesis) leads to insights for treatment of adipose-related diseases, such as obesity, coronary disease, and cancer, but has led to controversy among researchers, largely due to the complexity of the process. This paper reviews the recent literature on the genomic and non-genomic effects of GCs on WAT and BAT lipolysis and proposes research to address the many gaps in knowledge related to GC activity and its effects on disease.

Covid-19 & Obesity: Beyond Bmi

The pandemic of novel coronavirus disease 2019 (COVID-19) has triggered an international crisis resulting in excess morbidity and mortality with adverse societal, economic, and geopolitical consequences. Like other disease states, there are patient characteristics that impact clinical risk and determine the spectrum of severity. Obesity, or adiposity-based chronic disease, has emerged as an important risk factor for morbidity and mortality due to COVID-19. It is imperative to further stratify risk in patients with obesity to determine optimal mitigation and perhaps therapeutic preparedness strategies. We suspect that insulin resistance is an important pathophysiologic cause of poor outcomes in patients with obesity and COVID-19 independent of body mass index. This explains the association of type 2 diabetes mellitus (T2DM), hypertension (HTN), and cardiovascular disease with poor outcomes since insulin resistance is the main driver of both dysglycemia-based chronic disease and cardiometabolic-based chronic disease towards end-stage disease manifestations. Staging the severity of adiposity-related disease in a “complication-centric” manner (HTN, dyslipidemia, metabolic syndrome, T2DM, obstructive sleep apnea, etc.) among different ethnic groups in patients with COVID-19 should help predict the adverse risk of adiposity on patient health in a pragmatic and actionable manner during this pandemic.

The Role of miR-326 in Adipogenic Differentiation of Human Adipose-Derived Stem Cells by Targeting C/EBPα in vitro.

The CCAAT-enhancer-binding protein α (C/EBPα) plays an important role in adipogenic differentiation of adipose-derived stem cells (ASC). Recent studies have shown that microRNAs (miRNAs) participate in the regulation of self-renewal, proliferation, and multi-directional differentiation of ASCs. In the present study, we analyzed the targeting miRNAs on C/EBPα and found that miR-326 played an essential role in it. The results of qPCR confirmed that the expression of miR-326 was reduced in adipogenic differentiation. In addition, the dual-luciferase reporter assay system verified binding between miR-326 and the 3' untranslated region of C/EBPα. Furthermore, transfection of miR-326 into human adipose-derived stem cells caused a significant reduction in C/EBPα. Our results highlight the importance of miR-326 in adipogenic differentiation and provide a reliable basis for clinical treatment of adipose-related diseases. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:2054-2060, 2020. © 2019 American Association for Anatomy.

Expression regulation and functional analysis of RGS2 and RGS4 in adipogenic and osteogenic differentiation of human mesenchymal stem cells

BackgroundUnderstanding the molecular basis underlying the formation of bone-forming osteocytes and lipid-storing adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases. In this study, the role of RGS2 and RGS4, two members of the regulators of G protein signaling (RGS) family, was investigated during adipogenenic and osteogenenic differentiation of human mesenchymal stem cells (hMSCs).ResultsExpression of RGS2 and RGS4 were found to be inversely regulated during adipogenesis induced by dexamethasone (DEX) and 3-isobutyl-methylxanthine, regardless if insulin was present, with RGS2 up-regulated and RGS4 down-regulated in response to adipogenic induction. RGS2 expression was also up-regulated during osteogenesis at a level similar to that induced by treatment of DEX alone, a shared component of adipogenic and osteogenic differentiation inducing media, but significantly lower than the level induced by adipogenic inducing media. RGS4 expression was down-regulated during the first 48 h of osteogenesis but up-regulated afterwards, in both cases at levels similar to that induced by DEX alone. Expression knock-down using small interfering RNA against RGS2 resulted in decreased differentiation efficiency during both adipogenesis and osteogenesis. On the other hand, expression knock-down of RGS4 also resulted in decreased adipogenic differentiation but increased osteogenic differentiation.ConclusionsRGS2 and RGS4 are differentially regulated during adipogenic and osteogenic differentiation of hMSCs. In addition, both RGS2 and RGS4 play positive roles during adipogenesis but opposing roles during osteogenesis, with RGS2 as a positive regulator and RGS4 as a negative regulator. These results imply that members of RGS proteins may play multifaceted roles during human adipogenesis and osteogenesis to balance or counterbalance each other’s function during those processes.

Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial

BackgroundHigh-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption.MethodsUsing a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate.ResultsAt baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories).ConclusionConsuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis, lower leptin concentrations, and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease. However, between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made.Trial registrationNone.

Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach.

BackgroundThe link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.Methods and FindingsWe conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination.ConclusionsWe present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

A multiscale modeling framework for studying the mechanobiology of sarcopenic obesity.

An inactive sedentary lifestyle is a common risk factor contributing to sarcopenic obesity. At the cell scale, sustained mechanical deformations of the plasma membrane (PM) in adipocytes, characterizing chronic static loading in weight-bearing tissues during prolonged sitting or lying, were found to promote adipogenesis. Taking a mechanobiological perspective, we correlated here the macroscale mechanical deformations of weight-bearing adipose tissues (subcutaneous and intramuscular) with mechanical strains developing in the PMs of differentiating adipocytes. An innovative multiscale modeling framework for adipose tissues was developed for this purpose, where the buttocks, adipose tissues, adipocytes and the subcellular components: intracytoplasmic nucleus and lipid droplets as well as the PMs of the cells, were all represented. We found that a positive feedback loop very likely exists and is involved in the onset and progression of sarcopenic obesity, as follows. Adipogenesis in statically deformed adipocytes results in gaining more macroscopic subcutaneous and intramuscular fat mass, which then increases fat deformations macroscopically and microscopically, and hence triggers additional adipogenesis, and so on. Our present study is highly relevant in research of sarcopenic obesity and other adipose-related diseases such as diabetes, since mechanical distortion of adipocytes promotes adipogenesis and fat gain at the different dimensional scales.

Adipocyte Stiffness Increases with Accumulation of Lipid Droplets

Adipogenesis and increase in fat tissue mass are mechanosensitive processes and hence should be influenced by the mechanical properties of adipocytes. We evaluated subcellular effective stiffnesses of adipocytes using atomic force microscopy (AFM) and interferometric phase microscopy (IPM), and we verified the empirical results using finite element (FE) simulations. In the AFM studies, we found that the mean ratio of stiffnesses of the lipid droplets (LDs) over the nucleus was 0.83 ± 0.14, from which we further evaluated the ratios of LDs over cytoplasm stiffness, as being in the range of 2.5 to 8.3. These stiffness ratios, indicating that LDs are stiffer than cytoplasm, were verified by means of FE modeling, which simulated the AFM experiments, and provided good agreement between empirical and model-predicted structural behavior. In the IPM studies, we found that LDs mechanically distort their intracellular environment, which again indicated that LDs are mechanically stiffer than the surrounding cytoplasm. Combining these empirical and simulation data together, we provide in this study evidence that adipocytes stiffen with differentiation as a result of accumulation of LDs. Our results are relevant to research of adipose-related diseases, particularly overweight and obesity, from a mechanobiology and cellular mechanics perspectives.

Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trial

The susceptibility to type 2 diabetes of people of south Asian descent is established, but there is little trial-based evidence for interventions to tackle this problem. We assessed a weight control and physical activity intervention in south Asian individuals in the UK. We did this non-blinded trial in two National Health Service (NHS) regions in Scotland (UK). Between July 1, 2007, and Oct 31, 2009, we recruited men and women of Indian and Pakistani origin, aged 35 years or older, with waist circumference 90 cm or greater in men or 80 cm or greater in women, and with impaired glucose tolerance or impaired fasting glucose determined by oral glucose tolerance test. Families were randomised (using a random number generator program, with permuted blocks of random size, stratified by location [Edinburgh or Glasgow], ethnic group [Indian or Pakistani], and number of participants in the family [one vs more than one]) to intervention or control. Participants in the same family were not randomised separately. The intervention group received 15 visits from a dietitian over 3 years and the control group received four visits in the same period. The primary outcome was weight change at 3 years. Analysis was by modified intention to treat, excluding participants who died or were lost to follow-up. We used linear regression models to provide mean differences in baseline-adjusted weight at 3 years. This trial is registered, number ISRCTN25729565. Of 1319 people who were screened with an oral glucose tolerance test, 196 (15%) had impaired glucose tolerance or impaired fasting glucose and 171 entered the trial. Participants were in 156 family clusters that were randomised (78 families with 85 participants were allocated to intervention; 78 families with 86 participants were allocated to control). 167 (98%) participants in 152 families completed the trial. Mean weight loss in the intervention group was 1.13 kg (SD 4.12), compared with a mean weight gain of 0.51 kg (3.65) in the control group, an adjusted mean difference of -1.64 kg (95% CI -2.83 to -0.44). Modest, medium-term changes in weight are achievable as a component of lifestyle-change strategies, which might control or prevent adiposity-related diseases. National Prevention Research Initiative, NHS Research and Development; NHS National Services Scotland; NHS Health Scotland.

Associations of leg fat accumulation with adiposity‐related biological factors and risk of metabolic syndrome

The association between regional fat mass distribution and cardiometabolic risk factors has been inconsistent in the literature, and data for ethnic minority groups, such as non-Hispanic blacks and Hispanics, are lacking. We aimed to examine this association among 8802 US residents who participated in the 1999-2004 US National Health and Nutrition Examination Survey (NHANES). Body composition was measured using dual-energy X-ray absorptiometry (DXA). Leg fat indices included leg fat mass (FM), leg fat mass percent (FM%), leg to whole body FM ratio (leg/whole) and leg to trunk FM ratio (leg/trunk). We evaluated the correlation between leg fat indices and adiposity-related risk factors, as well as the association of these indices with metabolic syndrome (MetS). After adjusting for covariates including age, gender, and trunk FM or trunk FM%, higher leg FM and leg FM% were, in general, correlated favorably with adiposity-related risk factors and associated with lower odds of MetS in all ethnicities, including non-Hispanic whites and blacks and Hispanic groups. In addition, in all multivariate-adjusted models, leg/whole and leg/trunk ratios were strongly associated with lower levels of most risk factors and decreased odds of MetS in these ethnicities (all odds ratios comparing extreme quintiles < 0.1). Our results show that leg fat accumulation is inversely associated with adiposity-related biological factors and risk of MetS in both whites and ethnic groups, suggesting that regional fat distribution plays an important role in the etiology of adiposity-related diseases in these populations.

Stochastic Modeling of Adipogenesis in 3T3-L1 Cultures to Determine Probabilities of Events in the Cell’s Life Cycle

3T3-L1 preadipocytes are often being used in research of adipose-related diseases such as obesity, insulin resistance, and hyperlipidemia. We developed a stochastic model that simulated differentiation of four 3T3-L1 culture conditions distinct by the insulin concentration in the differentiation medium (2.5, 5, 7.5, or 10 μg/mL). The model simulated culture behavior and the accumulation of lipid droplets in the maturing cells from the day of induction of differentiation through 28 days after that. The cellular processes including cell adhesion, mitosis, growing after undergoing mitosis, commitment to the adipocyte lineage, and apoptosis were referred to as stochastic events in the modeling. By minimizing the error between our model and experimental results, we found that the probability for becoming committed to the adipocyte lineage in a single division and the probability for growing after undergoing mitosis were 0.02 and 0.8, respectively, regardless of the insulin concentration. The probability for undergoing mitosis was equal to 0.2 and 0.4 in cultures that had insulin concentrations of 2.5 and 5-10 μg/mL in the differentiation medium, respectively; hence the insulin concentration affected the probability for mitosis in the 3T3-L1 cells. The model and resulted probabilities now allow quantitative and visual predictions of adipogenesis in 3T3-L1 cultures, toward computational design of cell culturing protocols.

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats.

BackgroundMenopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT). This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to the decreased secretion of ovarian estrogens. Ovariectomy in rats and other animals is a commonly used model of menopause. It is well known that ovariectomy increases adiposity and that this can be reversed by estradiol treatment, but whether ovariectomy selectively increases IAAT has not been measured directly. Therefore, we used micro-computed tomography (microCT) to investigate this question in both chow-fed and dietary-obese rats.MethodsOvariectomized, ovariectomized and estradiol treated, and sham-operated (intact) rats were fed chow or chow plus Ensure (Abbott Nutrition; n = 7/group). Total (T) AT, IAAT and SAT were measured periodically by microCT. Regional distribution of AT was expressed as IAAT as a percentage of TAT (%IAAT). Excesses in these measures were calculated with respect to chow-fed intact rats to control for normal maturational changes. Chemical analysis of fat was done in chow-fed intact and ovariectomized rats at study end. Data were analyzed by t-tests and planned comparisons.ResultsBody mass, TAT, total fat mass, fat-free body mass, and %IAAT all increased in chow-fed intact rats during the 41 d study. In chow-fed rats, ovariectomy increased excess body mass, TAT, fat mass, fat-free body mass, and SAT, but had little effect on IAAT, in chow-fed rats, leading to a decrease in %IAAT. Ensure feeding markedly increased SAT, IAAT and TAT and did not significantly affect %IAAT. Ovariectomy had similar effects in Ensure-fed rats as in chow-fed rats, although less statistically reliable. Estradiol treatment prevented all the effects of ovariectomy.ConclusionsBoth ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases.

Positive Relationship Between Plasma Leptin Levels and Hypertension From an Epidemiological Perspective

It is well-documented that a higher body mass index (BMI) is associated with a greater risk of hypertension, even among those with a BMI within the “normal” range.1,2 Also, from the field of population sciences, it has been shown that it is a higher BMI caused by fat accumulation, and not by muscle growth, that is the problem. Thus, in a prospective study of >3000 subjects, it was a higher fat mass, and not a higher fat-free mass, that was associated with a greater risk of hypertension.2 So, how does fat tissue lead to hypertension? In this context, there has been a change in the way we look at the functions of fat tissue. The traditional view of fat tissue as a passive reservoir for energy storage is no longer valid.3 On the contrary, fat tissue is an active metabolic and endocrine organ that secretes hormones and cytokines with vascular and inflammatory effects.3 These hormones and cytokines are described as adipocytokines, and because of the close relationship between overweight and various diseases, these adipocytokines are regarded as possible intermediaries between fat tissue and adiposity-related diseases, including hypertension.4 Leptin is one such adipocytokine.3 Leptin is primarily secreted by fat cells in proportion to fat cell mass. Thus, in a human study, the correlation coefficient for the association between serum leptin levels and percentage of body fat was found to be as high as 0.85, a figure that was higher than the correlation coefficient found for the association between leptin levels and BMI ( r =0.66).5 So, no matter what functions leptin may have, the level of leptin will generally always be a good biomarker for the amount of body fat, which, as described above, is an important determinant of hypertension risk. In this context, it …

A Nuclear Receptor Atlas: 3T3-L1 Adipogenesis

The differentiation of a preadipocyte into a mature adipocyte represents a fundamental process in biology that requires a scripted program of transcriptional events leading to changes in gene expression. As part of our contribution to the Nuclear Receptor Signaling Atlas (NURSA), we used quantitative real-time PCR to profile the temporal expression of all 49 members of the mouse nuclear receptor superfamily at selected time points during differentiation of 3T3-L1 cells into mature, lipid-bearing adipocytes using two differentiation inducers [DMI (a cocktail of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin) and rosiglitazone]. We also included a comparative analysis of nuclear receptor expression in mouse primary preadipocytes and mature adipocytes. In addition to confirming the expression of receptors known to be required for adipogenesis, this analysis revealed the existence of a tightly regulated transcriptional cascade that appeared in three distinct temporal phases. The first phase began within 4 h of adipogenic initiation with the transient, sequential expression of four previously uncharacterized receptors, followed by biphasic expression of a second subset, and ended with the sequential increase in a third receptor subset over a period of 2 wk after initiation. The discovery that these receptors may serve as adipogenic biomarkers and as potential therapeutic targets in adipose-related diseases highlights the utility of quantitative expression profiling as a method for directing mechanism-based approaches to study complex regulatory pathways.