Fat Mass Obesity Research Articles

The Association of Serum Irisin with Impaired Glucose Before and After Laparoscopic Sleeve Gastrectomy in Obesity.

To demonstrate the association of irisin levels with impaired glucose before and after laparoscopic sleeve gastrectomy (LSG) in patients with obesity. Thirty-six patients with obesity undergoing LSG were included. We tested the irisin levels before and after LSG and conducted an evaluation of baseline irisin levels with elevated glucose as well as irisin changes with weight loss and its association with glucose control after LSG. Anthropometric measurements, body fat index, and metabolic parameters were significantly improved in 3months following LSG (all p < 0.05). Baseline irisin levels were significantly higher in obesity with elevated fasting glucose than that with normal glucose (2.98 [2.37, 3.63] vs. 3.72 [3.06, 5.32], p = 0.031). After adjustment for sex, gender, and body mass index (BMI), obesity with higher irisin levels was prone to have impaired fasting glucose (OR = 2.499, 95% CI = 1.047-5.964). According to receiver operating characteristic curve analysis, the diagnostic accuracy and sensitivity of baseline irisin levels on impaired fasting glucose were 75% and 77.8%. Irisin levels decreased from 3.29 (2.67, 4.43) to 2.82 (2.41, 3.25) ng/mL (p = 0.009) after LSG. The decreases of weight, BMI, and FFA were more in irisin changes group (△irisin ≥ 0.5) than in no irisin changes group (△irisin < 0.5). And △irisin was negatively associated with postprandial glucose (PG) at 3months after LSG (0.5h-PG, r = - 0.478, p = 0.029; 2h-PG, r = - 0.406, p = 0.017). Elevated baseline irisin levels indicated the impaired glucose in obesity. The decrease of irisin with weight loss provided more evidence for the contribution of serum irisin secretion by fat mass in obesity.

Association of an intronic SNP rs9939609 in FTO gene with type 2 diabetes mellitus among Bangladeshi population: A case–control study combined with updated meta-analysis

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder, caused by both genetic and environmental variables. The rs9939609 variant with a T > A mutation of the Fat mass obesity (FTO) gene has been known to have a strong association with T2DM and extensively investigated for its role in T2DM in different populations. In this study we conducted a case–control study based on the Bangladeshi population and a combined updated meta-analysis using the data of previous studies from different populations and our study to investigate the association of rs9939609 with T2DM. A total of 156 diabetic patients and 144 healthy non-diabetic controls were recruited. ARMS (Amplification Refractory Mutation System) PCR method was used for genotyping and sequencing was done to validate the PCR results. Our study found a significant association (p < 0.05) of rs9939609 with T2DM in co-dominant AA vs. TT (OR = 2.64) dominant TA + AA vs. TT (OR = 2.12) and additive 2(AA) + TA(OR = 2.224) genetic models. From the meta-analysis, we found significant association of rs9939609 with T2DM in the overall population for all genetic models. However, subgroup analysis showed negligible association in the Caucasian population unlike the Asian population. This is the first case–control study conducted on rs9939609 in the Bangladeshi population that revealed significant association with T2DM and also imply that the connection between them may be mediated by mechanisms other than obesity and increased BMI which was supported by results found in most of the Asian populations. This study could be used as a foundation for future association studies involving larger populations.

Smooth muscle cell FTO regulates contractile function.

The fat mass and obesity gene (FTO) is a N6-methyladenosine RNA demethylase that was initially linked by Genome-wide association studies to increased rates of obesity. Subsequent studies have revealed multiple mass-independent effects of the gene, including cardiac myocyte contractility. We created a mouse with a conditional and inducible smooth muscle cell deletion of Fto (Myh11 Cre+ Ftofl/fl) and did not observe any changes in mouse body mass or mitochondrial metabolism. However, the mice had significantly decreased blood pressure (hypotensive), despite increased heart rate and sodium, and significantly increased plasma renin. Remarkably, the third-order mesenteric arteries from these mice had almost no myogenic tone or capacity to constrict to smooth muscle depolarization or phenylephrine. Microarray analysis from Fto-/--isolated smooth muscle cells demonstrated a significant decrease in serum response factor (Srf) and the downstream effectors Acta2, Myocd, and Tagln; this was confirmed in cultured human coronary arteries with FTO siRNA. We conclude Fto is an important component to the contractility of smooth muscle cells.NEW & NOTEWORTHY We show a key role for the fat mass obesity (FTO) gene in regulating smooth muscle contractility, possibly by methylation of serum response factor (Srf).

Comprehensive mutations analyses of FTO (fat mass and obesity-associated gene) and their effects on FTO's substrate binding implicated in obesity.

An excessive amount of fat deposition in the body leads to obesity which is a complex disease and poses a generic threat to human health. It increases the risk of various other diseases like diabetes, cardiovascular disease, and multiple types of cancer. Genomic studies have shown that the expression of the fat mass obesity (FTO) gene was highly altered and identified as one of the key biomarkers for obesity. This study has been undertaken to investigate the mutational profile of the FTO gene and elucidates its effect on the protein structure and function. Harmful effects of various missense mutations were predicted using different independent tools and it was observed that all mutations were highly pathogenic. Molecular dynamics (MD) simulations were performed to study the structure and function of FTO protein upon different mutations and it was found that mutations decreased the structure stability and affected protein conformation. Furthermore, a protein residue network analysis suggested that the mutations affected the overall residues bonding and topology. Finally, molecular docking coupled with MD simulation suggested that mutations affected FTO substrate binding by changing the protein-ligand affinity. Hence, the results of this finding would help in an in-depth understanding of the molecular biology of the FTO gene and its variants and lead to the development of effective therapeutics against associated diseases and disorders.

AN UPDATED REVIEW IN CORRELATING FAT MASS OBESITY ASSOCIATED GENETIC POLYMORPHISM IN WOMEN WITH POLYCYSTIC OVARIAN CONDITIONS

Women with Polycystic ovarian condition (PCOS) are reported to have obesity, which essentially influences the disorder's associated with insulin resistance, type 2 diabetes and cardiovascular disorders. PCOS is a problem of endocrine abnormality in women between the ages of 14-44. In this paper we review on recent methods in genotyping of fat mass obesity (FTO) associated gene single nucleotide polymorphism and its relationship with PCOS. Literature survey indicated that in diagnosis of PCOS, blood tests were normally used in gene polymorphism investigations and DNA tests were used for genotyping examination. The quick detection by polymerase chain reaction (PCR) amplification is one of the commonest tests for identifying single nucleotide polymorphism (SNP) for FTO traits which is being routinely used to understand the frequency of SNP polymorphism in a given set of population in various countries and in ethnic groups. Worldwide, extensive investigations were carried out to analyze the genotypes of FTO traits and its association in understanding the etiology of PCOS. Such literature surveys are beneficial in developing simple PCOS diagnostic methods and finding new approaches in therapeutic interventions. In this review paper, we highlight the genetic basis and importance of testing the FTO parameter in understanding the pathogenesis and the management of PCOS.

Multipotent Stromal Cells from Subcutaneous Adipose Tissue of Normal Weight and Obese Subjects: Modulation of Their Adipogenic Differentiation by Adenosine A1 Receptor Ligands.

Adenosine A1 receptor (A1R) activation, stimulating lipogenesis and decreasing insulin resistance, could be useful for metabolic syndrome management in obese subjects. Since full A1R agonists induce harmful side-effects, while partial agonists show a better pharmacological profile, we investigated the influence of two derivatives of the full A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA), C1 and C2 behaving as A1R partial agonists in animal models, on the adipogenic differentiation of stromal/stem cells (ASCs) from human subcutaneous adipose tissue, which mainly contribute to increase fat mass in obesity. The ASCs from normal-weight subjects showed increased proliferation and A1R expression but reduced adipogenic differentiation compared to obese individual-derived ASCs. Cell exposure to CCPA, C1, C2 or DPCPX, an A1R antagonist, did not affect ASC proliferation, while mainly C2 and DPCPX significantly decreased adipogenic differentiation of both ASC types, reducing the activity of glycerol-3-phosphate dehydrogenase and the expression of PPARγ and FABP-4, all adipogenic markers, and phosphorylation of Akt in the phosphatidylinositol-3-kinase pathway, which plays a key-role in adipogenesis. While requiring confirmation in in vivo models, our results suggest that A1R partial agonists or antagonists, by limiting ASC differentiation into adipocytes and, thereby, fat mass expansion, could favor development/worsening of metabolic syndrome in obese subjects without a dietary control.

Abstract 11483: A 7-Year Arterial Stiffness and Carotid Intima-Media Thickness Progression Predict Obesity, High Lean Mass, and Incident Hypertension from Age 17.7 to 24.5 Years: the ALSPAC Study

Introduction: An American Heart Association’s statement recommended investigating the natural history of arterial stiffness and blood pressure (BP) vis-à-vis the rate at which arterial stiffness and BP increase with age. Hypothesis: To test whether carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression independently predict increased fat mass and BP. Methods: We studied 3862 participants from the Avon Longitudinal Study of Parents and Children birth cohort. cfPWV and cIMT were measured by ultrasound scan, total and trunk fat mass, and lean mass by dual-energy Xray absorptiometry scan, body mass index (BMI), BP, heart rate, fasting insulin, glucose, high sensitivity C-reactive protein, and lipid profile were measured at ages 17.7 and 24.5 years. Participants at &gt;75th percentile of total and trunk fat mass or having &gt;24.9 kg/m 2 BMI were classified as overweight and obese, &gt;75th percentile as high lean mass, and &gt;120/80 mm Hg as elevated BP and hypertension. Data were analysed with logistic regression and linear mixed models, adjusting for cardiometabolic and lifestyle factors. Results: Among 1719 [44.5%] male and 2143 [55.5%] female participants, cfPWV at 17.7 years independently predicted systolic hypertension [Odds ratio (OR) 1.19 (1.01 - 1.40); p=0.043], diastolic hypertension [OR 1.77 (1.32 - 2.38); p&lt;0.0001], BMI-obesity [OR 1.19 (1.01 - 1.41); p=0.041], and trunk fat mass-obesity [OR 1.24 (1.03 - 1.49); p=0.023] at age 24.5 years. cIMT at 17.7 years predicted high lean mass [OR 54.29 (0.73 - 4053.52); p=0.069] at 24.5 years with borderline significance. A 7-year increase in cfPWV was directly associated with the 7-year increase in lean mass [Effect estimate 0.09 kg (0.05 - 0.13); p&lt;0.0001], systolic BP [21.58 mmHg (14.32 - 28.84); p&lt;0.0001] and diastolic BP [31.74 mmHg (24.90 - 38.57); p&lt;0.0001], but inversely associated with BMI [-0.03 kg/m 2 (-0.06 - -0.01); p=0.039]. cIMT progression from age 17.7 - 24.5 years was directly associated with the 7-year increase in total fat mass, trunk fat mass, lean mass, BMI, and diastolic BP. Conclusions: Arterial stiffness and cIMT progression independently predicted obesity, high lean mass, and incident hypertension among young adults.

Polycystic ovary syndrome is linked with the fat mass obesity (FTO) gene variants rs17817449 and rs1421085 in western Saudi Arabia.

Polycystic ovary syndrome (PCOS) is characterised by infertility, obesity, insulin resistance and clinical and/or biochemical signs of hyperandrogenism. Obesity is known to be correlated with PCOS causing ovulatory dysfunction and hormone imbalances. Moreover, fat mass and the obesity gene (FTO) were linked with obesity and PCOS. Therefore, it is of interest to determine the genotype and allele frequency for three FTO variants - rs17817449 (G/T), rs1421085 (C/T) and rs8050136 (A/C) -in western Saudi population. 95 PCOS patients and 94 controls were recruited for this study. The genetic variants were assayed using real-time polymerase chain reaction using TaqMan genotyping assays. The chi-squared test was applied to investigate the difference between single nucleotide polymorphisms on PCOS and control subjects, and binary logistic regression was used to determine the association of FTO variants with PCOS symptoms. Variants rs17817449 and rs1421085 were significantly linked with PCOS susceptibility in the study population. Rs17817449 and rs8050136 were significantly associated with hair loss in the PCOS group. Furthermore, rs1421085 and rs8050136 were associated with a high body mass index (BMI>30 kg/m2). Risk alleles in our population associated with hair loss and elevated BMI in women with PCOS were homozygous C for rs8050136. This data will help in defining the genetic predisposition of PCOS among women in western Saudi Arabia.

Frequency distribution and association of Fat-mass and obesity (FTO) gene SNP rs-9939609 variant with Diabetes Mellitus Type-II population of Hyderabad, Sindh, Pakistan.

Background/AimDiabetes Mellitus (DM) is one of the important public health issues worldwide. The Fat mass obesity (FTO) gene rs-9939609 variant identified single nucleotide polymorphism (SNP) with the T to A missense mutation, and has a strong association with T2DM. FTO gene is present on chromosome “16q12.2” comprising of nine exons. FTO gene rs-9939609 a variant is commonly found in the Pakistani Population. The purpose of the study was to alert the population about the rs-9939609 variant SNP, having a strong association with T2DM.Material and MethodsTotal of 190 participants were included in the present cross-sectional study. To collect the samples non-probability convenience technique was used. subjects were recruited and divided into three groups, normal healthy subjects, obese and T2DM. The patients were selected from the Medicine department Jamshoro/Hyderabad by filling the pre-designed proforma, as well as verbal and written consent taken from study participants. To analysed the data ANOVA Post hoc (Tukey-test) was applied for comparison among groups (P < 0.05) and “SNP-STAT” online software was used for frequencies.ResultsThe BMI, neck circumference, waist circumference and lipid profile, fasting blood sugar and HbA1c was found significant (p < 0.001) in both genders as compared to control. Homozygous and heterozygous distribution of allelic and genotyping frequency was found in study participants. 37.9 %T/A, 57.4% T/T, and A/A were 4.7%. The FTO gene rs-9939609 variant amplified and have an increased risk of developing T2DM in the Sindh population. Codominant model odd ratio of T/A showed 2.42 (CI)1.23–3.84, with significant p < 0.032.ConclusionThe present study concluded that the FTO gene SNP rs-9939609 variant was found in the population of Hyderabad, Sindh and having strong association with T2DM and obese individuals. Increase BMI, neck and waist circumference are the biomarkers of obesity and causative factors of T2DM.

Variants in the Obesity-Linked FTO gene locus modulates psychopathological features of patients with Anorexia Nervosa.

Our aim was to determine whether variability in the fat mass obesity (FTO) gene locus, consistently related to obesity, affects the risk of eating disorders (ED) and/or the psychopathology displayed by these patients. We analyzed 26 tag-single nucleotide polymorphisms (SNPs) that capture FTO variability in 352 ED patients [233 with Anorexia Nervosa (AN) and 119 with binge-eating] and 396 controls. Psychopathological symptoms and traits were evaluated by the Eating Disorders Inventory Test 2 (EDI-2) and Symptoms Checklist 90 Revised (SCL-90R) questionnaires. No associations were found for ED risk. The rs7205987 CC genotype correlated with higher scores in all but one of the EDI-2 scales in the AN group. Associations with Bulimia (p=0.0019) and Interoceptive Awareness (p=0.00007) retained significance after False Discovery Rate (FDR) correction for multiple testing. A 3-SNP sliding window analysis showed that FTO haplotypes were again highly associated with Interoceptive Awareness (rs9921255/rs6499662/rs7205987 haplotype; FDR-q=0.04), Bulimia (rs1125338/rs2192872/rs708258; FDR-q=0.00037), and Maturity Fears (rs708258/rs12599672/rs11076017; FDR-q=0.041). In addition, a distal region of the gene between rs9924877 (position 53947509) and rs2192872 (54040715) was linked to Anxiety, Depression and Phobic Anxiety in AN patients, with FDR-q values ranging from 0.023 to 0.045. The results suggest that the FTO gene might be an important locus regarding traits and psychopathological symptoms often displayed by AN patients.

The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients

Obesity is a well-known risk factor for multiple diseases including multiple sclerosis (MS). Polymorphisms in the fat-mass obesity (FTO) gene have been consistently found to be associated with obesity, and recently found to increase the risk of developing MS. We therefore assessed the common FTO gene polymorphism (rs9939609) in relation to obesity, risk of developing MS and its disability in a cohort of MS patients. A cohort of 200 MS patients (135 females and 65 males) were genotyped for the FTO rs9939609 polymorphism. Using both logistic and linear regression we assessed the relationship between the variant and the selected phenotypes under both an additive and recessive genetic models. The A-allele was found to be associated with being overweight/obese in MS patients (OR = 2.48 (95% CI 1.17–5.29); p = 0.01). In addition, The A-allele was also found to be associated with increased MS disability (β = 0.48 (95% CI 0.03–0.92); p = 0.03). However, no association was found with risk of developing MS (p > 0.05). Moreover, our association with obesity is consistent with previous reports, whereas the association with disability is novel and warrants further investigation on the role of FTO in disease progression.

Exposure of Fat Mass Obesity Gene Polymorphism in Diabetes Mellitus Type-II Females of Hyderabad, Sindh

OBJECTIVES: To analyse and compare fat mass obesity gene polymorphism from blood samples in females with T2DM and Non-diabetic healthy females in population of Hyderabad, Sindh.METHODOLOGY: Across sectional comparative study was conducted at Institute of Biotechnology and Genetic Engineering University of Sindh, Jamshoro. The patients were recruited from Department of Medicine unit-II (LUH) Jamshoro/Hyderabad while non-Diabetic healthy females were recruited from society by filling Performa. The verbal and written consent was taken from all participants and explaining them about purpose of study. Finallyblood sample for gene analysis and other biochemical tests were collected and stored in the laboratory at -20C. Total 100 females were included in this study out of which 50 were T2DM females and 50 were normal healthy females.RESULTS: FTO (fat mass obesity) gene has strong association with basal metabolic index (BMI), as BMI increases the risk of T2DM in females also increases. We observed minor allele A and T at rs9939609 in Type 2 diabeticfemales with significantly higher with difference of (p &lt;0.05) as compared with control group.In the present study rs9939609 FTO variant is strongly associated with Type 2Diabeticfemales of Hyderabad, Sindh. CONCLUSION: In the present study rs9939609 FTO variant was strongly associated with Type 2 Diabetic females of Hyderabad, Sindh. The study was also aimed to aware the population about inherited FTO gene variant which might be possible to implement genetic screening of females with T2DM which will be help in prevention of T2DM in future. KEY WORDS: FTO gene, T2DM, BMI, ARMS PCR, Electrophoresis

The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis

ObjectivesObesity is characterized by excessive fat mass and is associated with serious diseases such as type 2 diabetes. Targeting excess fat mass by sustained lipolysis has been a major challenge for anti-obesity therapies due to unwanted side effects. TLQP-21, a neuropeptide encoded by the pro-peptide VGF (non-acronymic), that binds the complement 3a receptor 1 (C3aR1) on the adipocyte membrane, is emerging as a novel modulator of adipocyte functions and a potential target for obesity-associated diseases. The molecular mechanism is still largely uncharacterized. MethodsWe used a combination of pharmacological and genetic gain and loss of function approaches. 3T3-L1 and mature murine adipocytes were used for in vitro experiments. Chronic in vivo experiments were conducted on diet-induced obese wild type, β1, β2, β3-adrenergic receptor (AR) deficient and C3aR1 knockout mice. Acute in vivo lipolysis experiments were conducted on Sprague Dawley rats. ResultsWe demonstrated that TLQP-21 does not possess lipolytic properties per se. Rather, it enhances β-AR activation-induced lipolysis by a mechanism requiring Ca2+ mobilization and ERK activation of Hormone Sensitive Lipase (HSL). TLQP-21 acutely potentiated isoproterenol-induced lipolysis in vivo. Finally, chronic peripheral TLQP-21 treatment decreases body weight and fat mass in diet induced obese mice by a mechanism involving β-adrenergic and C3a receptor activation without associated adverse metabolic effects. ConclusionsIn conclusion, our data identify an alternative pathway modulating lipolysis that could be targeted to diminish fat mass in obesity without the side effects typically observed when using potent pro-lipolytic molecules.

Reversible RNA Methylation In Gene Expression Regulation

We have discovered the first two RNA demethylases: FTO, a protein associated with human fat mass obesity and development, and ALKBH5, a protein that affects spermatogenesis in a mouse model. These two proteins catalyze oxidative demethylation of the most prevalent internal modifications of mammalian messenger RNA (mRNA) and other nuclear RNA, N6‐methyladenosine (m6A). These results indicate that reversible RNA modification could impact biological regulation analogous to the well‐known reversible DNA and histone chemical modifications. We have also identified and characterized proteins that can selectively recognize m6A‐modified mRNA and affect the translation status and lifetime of the target mRNA, as well as molecular machines that deposit the m6A methylation on nuclear RNA. Our discoveries indicate the presence of a new mode of biological regulation that depends on reversible and dynamic RNA modifications.

Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment.

Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO’s (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggesting a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA ‘epimark’ remain to be discovered. There is supportive evidence that m6A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells.The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6A could function alternatively to being a degradation mark in S. cerevisiae; we also sought to test whether it can be induced under non-standard sporulation conditions. We find a positive association between the presence of m6A and message translatability. We also find m6A induction following prolonged rapamycin treatment.

Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.

Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance.

Effect of Nutritional Regulation on Adipokines in Obesity: A Review

Childhood obesity has become a major public health problem worldwide and it increases the risk of developing severe obesity, coronary heart disease, type 2 diabetes and respiratory disease in adulthood. Low grade inflammation has been identified as a key factor in development of obesity. In obesity, the expanding adipose tissue makes a substantial contribution to the development of obesity-linked inflammation via dysregulated secretion of pro-inflammatory cytokines, chemokines and adipokines and the reduction of anti-inflammatory adipokines, such as adiponectin. The macronutrient composition of the diet regulates the overall body weight and metabolism and caloric intake is one of the major contributors to obesity, where certain kinds of diet (pro-inflammatory) can promote obesity, and other kinds (anti-inflammatory) can reduce it. Lifestyle interventions like caloric restriction and increases in physical activity can lead to weight control which induce attenuation of obesity-induced inflammatory responses, which is a risk factor for obesity related chronic diseases, along with a decrease in fat mass in obesity.

Adipose Tissue Overexpression of Vascular Endothelial Growth Factor Protects Against Diet-Induced Obesity and Insulin Resistance

During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adipose tissue (BAT) and white adipose tissue (WAT) were generated. Vessel formation, metabolism, and inflammation were studied in VEGF transgenic mice and wild-type littermates fed chow or a high-fat diet. Overexpression of VEGF resulted in increased blood vessel number and size in both WAT and BAT and protection against high-fat diet–induced hypoxia and obesity, with no differences in food intake. This was associated with increased thermogenesis and energy expenditure. Moreover, whole-body insulin sensitivity and glucose tolerance were improved. Transgenic mice presented increased macrophage infiltration, with a higher number of M2 anti-inflammatory and fewer M1 proinflammatory macrophages than wild-type littermates, thus maintaining an anti-inflammatory milieu that could avoid insulin resistance. These studies suggest that overexpression of VEGF in adipose tissue is a potential therapeutic strategy for the prevention of obesity and insulin resistance.

Obesity and childhood survivors of acute lymphoblastic leukemia: Do genetics play a role?

Childhood survivors of acute lymphoblastic leukemia (ALL) are increased risk of several chronic complications, such as second cancers, pulmonary, metabolic complications and cardiovascular disease. Obesity and metabolic syndrome is one of the most common treatment related complication in children surviving cancer, which concurs with our nations childhood epidemic [1-3] Recent research has identified the role of genetics in the development of obesity and metabolic syndrome in childhood survivors of ALL. Growth hormone deficiency, Leptin regulation, fat mass obesity (FTO) gene and the insulin resistant ENPP1 variants disorders has been associated adverse effects of chemotherapeutic treatment and the cause of clinical manifestations of metabolic syndrome [4-8]. The illumination of the role of genetic variants can shed insights into obesity within high risk population, as well as, a target to prevent disease.

Subcutaneous Adipose Tissue from Obese and Lean Adults Does Not Release HepcidinIn Vivo

Hepcidin is the main regulator of systemic iron homeostasis and is primarily produced by the liver but is also expressed, at the mRNA-level, in periphery tissues including the subcutaneous and visceral adipose tissue. Obesity is associated with elevated hepcidin concentrations and iron depletion suggesting that the exaggerated fat mass in obesity could contribute significantly to circulating hepcidin levels consequently altering iron homeostasis. The objective of this study was to determine if abdominal subcutaneous adipose tissue (AbScAT) releases hepcidin in vivo and if release is modified by obesity. Arterio-venous differences in concentrations of hepcidin were measured across AbScAT in 9 obese and 9 lean adults. Overall (n = 18), mean plasma hepcidin concentrations were significantly higher in arterialized compared to AbScAT venous samples [mean difference (arterialized-AbScAT venous plasma hepcidin) = 4.9 ± 9.6 ng/mL, P = 0.04]. Net regional release was not calculated because mean venous plasma hepcidin concentrations were lower than mean arterialized concentrations indicating no net release. Significant correlations between AbScAT venous and arterialized plasma hepcidin concentrations with anthropometric variables were not observed. Findings from this vein drainage study suggest there is no net release of hepcidin from the AbScAT depot and thereby no ability to signal systemically, even in obesity.