Oroxylum indicum (L.) Kurz extract inhibits adipogenesis and lipase activity in vitro

Background: Oroxylum indicum (L.) Kurz (O. indicum) is found in Thailand. It has been used for the treatment of obesity. This study aimed to investigate the effects of an O. indicum extract (OIE) on the adipogenic and biomolecular change in 3T3-L1 adipocytes. Methods: Initial studies examined the chemical components of OIE. The cell line 3T3-L1 was used to establish potential toxic effects of OIE during the differentiation of pre-adipocytes to adipocytes. The inhibitory effect of OIE on lipid accumulation in 3T3-L1 cells was investigated. Moreover, the impact of OIE on pancreatic lipase activity was determined. In further experiments, Fourier Transform Infrared (FTIR) was used to monitor and discriminate biomolecular changes caused by the potential anti-adipogenic effect of OIE on 3T3-L1 cells. Results: Chemical screening methods indicated that OIE was composed of flavonoids, alkaloids, steroids, glycosides, and tannins. The percentage viability of 3T3-L1 cells was not significantly decreased after exposure to either 200 or 150 μg/mL of OIE for 2 and 10 days, respectively compared to control cells. The OIE exhibited a dose-dependent reduction of lipid accumulation compared to the control (p < 0.05). The extract also demonstrated a dosedependent inhibitory effect upon lipase activity compared to the control. The inhibitory effect of the OIE on lipid accumulation in 3T3-L1 cells was also confirmed using FTIR microspectroscopy. The signal intensity and the integrated areas relating to lipids, lipid esters, nucleic acids, glycogen and carbohydrates of the OIE-treated 3T3-L1 adipocytes were significantly lower than the non-treated 3T3-L1 adipocytes (p < 0.05). Principal component analysis (PCA) indicated four distinct clusters for the FTIR spectra of 3T3-L1 adipocytes based on biomolecular changes (lipids, proteins, nucleic acids, and carbohydrates). This observation was confirmed using Unsupervised hierarchical cluster analysis (UHCA). Conclusions: These novel findings provide evidence that the OIE derived from the fruit pods of the plant is capable of inhibiting lipid and carbohydrate accumulation in adipocytes and also has the potential to inhibit an enzyme associated with fat absorption. The initial observations indicate that OIE may have important properties which in the future may be exploited for the management of the overweight or obese

Expression of genes related to prostaglandin synthesis or signaling in human subcutaneous and omental adipose tissue: depot differences and modulation by adipogenesis

Objectives. (1) To examine depot-specific PGE2 and PGF2α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2) to identify changes in expression of these transcripts through preadipocyte differentiation; and (3) to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements. Methods. Fat samples were obtained surgically in women. PGE2 and PGF2α release by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR. Results. Cultured preadipocytes and explants from omental fat released more PGE2 and PGF2α than those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments ( for all). Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements. Conclusion. Cells from the omental fat compartment release more PGE2 and PGF2α than those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts. 1. Introductio

Obesity and male breast cancer: Provocative parallels?

While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21st century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence

Expression of Genes Related to Prostaglandin Synthesis or Signaling in Human Subcutaneous and Omental Adipose Tissue: Depot Differences and Modulation by Adipogenesis

Objectives. (1) To examine depot-specific PGE2 and PGF2α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2) to identify changes in expression of these transcripts through preadipocyte differentiation; and (3) to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements. Methods. Fat samples were obtained surgically in women. PGE2 and PGF2α release by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR. Results. Cultured preadipocytes and explants from omental fat released more PGE2 and PGF2α than those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments (P≤0.01 for all). Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements. Conclusion. Cells from the omental fat compartment release more PGE2 and PGF2α than those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts

Adipose Tissue Endothelial Cells From Obese Human Subjects: Differences Among Depots in Angiogenic, Metabolic, and Inflammatory Gene Expression and Cellular Senescence

International audienceOBJECTIVE: Regional differences among adipose depots in capacities for fatty acid storage, susceptibility to hypoxia, and inflammation likely contribute to complications of obesity. We defined the properties of endothelial cells (EC) isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) biopsied in parallel from obese subjects. RESEARCH DESIGN AND METHODS: The architecture and properties of the fat tissue capillary network were analyzed using immunohistochemistry and flow cytometry. CD34(+)/CD31(+) EC were isolated by immunoselection/depletion. Expression of chemokines, adhesion molecules, angiogenic factor receptors, as well as lipogenic and senescence-related genes were assayed by real-time PCR. Fat cell size and expression of hypoxia-dependent genes were determined in adipocytes from both fat depots. RESULTS: Hypoxia-related genes were more highly expressed in VAT than SAT adipocytes. VAT adipocytes were smaller than SAT adipocytes. Vascular density and EC abundance were higher in VAT. VAT-EC exhibited a marked angiogenic and inflammatory state with decreased expression of metabolism-related genes, including endothelial lipase, GPIHBP1, and PPAR gamma. VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and γ-H2AX, and decreased expression of SIRT1. Exposure to VAT adipocytes caused more EC senescence-associated β-galactosidase activity than SAT adipocytes, an effect reduced in the presence of vascular endothelial growth factor A (VEGFA) neutralizing antibodies. CONCLUSIONS: VAT-EC exhibit a more marked angiogenic and proinflammatory state than SAT-EC. This phenotype may be related to premature EC senescence. VAT-EC may contribute to hypoxia and inflammation in VAT

The HERITAGE Family Study: A Review of the Effects of Exercise Training on Cardiometabolic Health, with Insights into Molecular Transducers

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative-omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study

DUSP1

The DUSP1 gene encodes a member of the dual-specificity phosphatase family previously identified as being differentially expressed in visceral adipose tissue (VAT) of severely obese men with versus without the metabolic syndrome. Objective. To test the association between DUSP1 polymorphisms, obesity-related metabolic complications, gene methylation, and expression levels in VAT. Methods. The DUSP1 locus and promoter region were sequenced in 25 individuals. SNPs were tested for association with obesity-related complications in a cohort of more than 1900 severely obese individuals. The impact of SNPs on methylation levels of 36 CpG sites and correlations between DNA methylation and gene expression levels in VAT were computed in a subset of 14 samples. Results. Heterozygotes for rs881150 had lower HDL-cholesterol levels (HDL-C; P = 0.01), and homozygotes for the minor allele of rs13184134 and rs7702178 had increased fasting glucose levels (P = 0.04 and 0.01, resp.). rs881150 was associated with methylation levels of CpG sites located ~1250 bp upstream the transcription start site. Methylation levels of 4 CpG sites were inversely correlated with DUSP1 gene expression. Conclusion. These results suggest that DUSP1 polymorphisms modulate plasma glucose and HDL-C levels in obese patients possibly through alterations of DNA methylation and gene expression levels

Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women

WSTĘP. Autorzy sprawdzili słuszność hipotezy zakładającej, że związany z wiekiem przyrost tkanki tłuszczowej trzewnej odpowiada częściowo za ujemny wpływ na insulinowrażliwość i profil lipidowy u kobiet bez otyłości. MATERIAŁ I METODY. Bezpośrednio oceniono: powierzchnię podskórnej i trzewnej tkanki tłuszczowej (tomografia komputerowa), zużycie glukozy (badanie metodą hiperinsulinowej/euglikemicznej klamry metabolicznej), elementy składowe organizmu (metoda absorpcjometrii promieniami X dwoistej energii), profil lipidowy oraz maksymalne zużycie tlenu (VO2max) u 178 kobiet bez otyłości, zakwalifikowanych do odpowiednich grup wiekowych: grupa 1 - 28 &plusmn; 4 lata (n = 88); grupa 2 - 46 &plusmn; 2 lata (n = 38); grupa 3 - 53 &plusmn; 2 lata (n = 31); grupa 4 - 67 &plusmn; 6 lat (n = 21). WYNIKI. Powierzchnia trzewnej tkanki tłuszczowej zwiększa się wraz z wiekiem (2,36 cm2 rocznie, p < 0,0001). Zanotowano związany z wiekiem wzrost stężenia cholesterolu całkowitego (p < 0,0003), triglicerydów (p < 0,0009), cholesterolu frakcji LDL (p < 0,027) i stosunku stężenia cholesterolu całkowitego do cholesterolu frakcji HDL (p < 0,042). Obserwowane różnice w insulinowrażliwości także wiązały się z wiekiem, jednakże w tym przypadku zależność była odmienna. Insulinowrażliwość, wyrażona jako całkowita lub przeliczona na kilogram beztłuszczowej masy ciała, była najniższa w grupie 4, ale nie różniła się istotnie między grupami 1, 2 i 3. Po analizie statystycznej, uwzględniającej powierzchnię tkanki tłuszczowej trzewnej, niższa insulinowrażliwość utrzymywała się, jednocześnie, relatywnie zmniejszyła się różnica w porównaniu z pozostałymi grupami. Wpływ zawartości trzewnej tkanki tłuszczowej na związane z wiekiem zmiany profilu lipidowego był silniejszy. Różnice w powierzchni trzewnej i głębokiej podskórnej tkanki tłuszczowej znosiły wpływ wieku na stężenie cholesterolu całkowitego, triglicerydów i cholesterolu frakcji LDL. Nie obserwowano natomiast wpływu wartości VO2max lub aktywnego wypoczynku na zależne od wieku zmiany w insulinowrażliwości bądź profilu lipidowym. WNIOSKI. 1) Wraz z wiekiem zwiększa się powierzchnia trzewnej tkanki tłuszczowej, podczas gdy zmniejszenie insulinowrażliwości obserwuje się tylko u kobiet starszych; 2) Związane z wiekiem różnice w trzewnej tkance tłuszczowej tylko w niewielkim stopniu odpowiadają za spadek insulinowrażliwości u kobiet bez otyłości; 3) Niepożądane zmiany profilu lipidowego w dużym stopniu wiążą się z zależnym od wieku przyrostem trzewnej tkanki tłuszczowej.INTRODUCTION. We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women. MATERIAL AND METHODS. We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (VO2max) in 178 nonobese women categorized into four age groups: group 1, 28 &plusmn; 4 years, n = 88; group 2, 46 &plusmn; 2 years, n = 38; group 3, 53 &plusmn; 2 years, n = 31; and group 4, 67 &plusmn; 6 years, n = 21. RESULTS. Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, agerelated changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on agerelated changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of VO2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood-lipid profile were noted. CONCLUSIONS. We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue