Endophilin A2: A Potential Link to Adiposity and Beyond

Alfadda, Assim A.,Sallam, Reem M.,Gul, Rukhsana,Hwang, Injae,Ka, Sojeong Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.11

Adipose tissue plays a central role in regulating dynamic cross-talk between tissues and organs. A detailed description of molecules that are differentially expressed upon changes in adipose tissue mass is expected to increase our understanding of the molecular mechanisms that underlie obesity and related metabolic co-morbidities. Our previous studies suggest a possible link between endophilins (SH3Grb2 proteins) and changes in body weight. To explore this further, we sought to assess the distribution of endophilin A2 (EA2) in human adipose tissue and experimental animals. Human paired adipose tissue samples (subcutaneous and visceral) were collected from subjects undergoing elective abdominal surgery and abdominal liposuction. We observed elevated EA2 gene expression in the subcutaneous compared to that in the visceral human adipose tissue. EA2 gene expression negatively correlated with adiponectin and chemerin in visceral adipose tissue, and positively correlated with $TNF-{\alpha}$ in subcutaneous adipose tissue. EA2 gene expression was significantly downregulated during differentiation of preadipocytes in vitro. In conclusion, this study provides a description of EA2 distribution and emphasizes a need to study the roles of this protein during the progression of obesity.

A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients

Alfadda, Assim A.,Masood, Afshan,Al-Naami, Mohammed Y.,Chaurand, Pierre,Benabdelkamel, Hicham Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.9

Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood. In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, $p{\leq}0.05$) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the $NF{\kappa}B$, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.

Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

Assim A Alfadda,Reem M Sallam,Muhammad Azhar Chishti,Amr S Moustafa,Sumbul Fatma,Waleed S Alomaim,Mohammed Y Al-Naami,Abdulelah F Bassas,George P Chrousos,Hyunsun Jo 한국분자세포생물학회 2012 Molecules and cells Vol.33 No.6

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentia-tion and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Assim A Alfadda,Sumbul Fatma,M Azhar Chishti,Mohammed Y Al-Naami,Ruba Elawad,Carmen Deanna O Mendoza,Hyunsun Jo,이윤석 한국분자세포생물학회 2012 Molecules and cells Vol.33 No.1

Obesity is associated with chronic low-grade inflamma-tion, which contributes to systemic metabolic irregularities and obesity-linked metabolic disorders. Orosomucoid (ORM), an acute phase reactant protein, was shown to be produced in response to metabolic and inflammatory signals in the adipose tissue of obese mice, which protects them from severe inflammation and subsequent metabolic dysfunction. In this study, we examined whether there are site-specific differences between visceral and subcutaneous adipose tissue (VAT and SAT, respectively) ORM gene and protein expression from individuals with a wide range of obesity and the relationship between expressed and circulating ORM levels and measures of adiposity, insulin resistance, and pro- and anti-inflammatory markers and adipokines. The level of circulating ORM correlated positively with BMI, body fat mass, and serum leptin. It also correlated with fasting insulin, HOMA-IR values and C-reactive protein in men. There were no site-specific differences in ORM mRNA and protein expression between VAT and SAT, nor did we find a relationship between circulating ORM levels and its mRNA expression in either fat depot. We found that ORM mRNA expression correlated with mRNA expression of TNF-, IL-6, and adiponectin in VAT, and with TNF- and adiponectin in SAT. These observations are the first description linking adipose tissue ORM and pro- and anti-inflammatory molecules in humans. The close links of ORM and measures of adiposity, insulin resistance, and adipose tissue inflammation in humans reinforce previous experimental data and warrant further studies to explore a possible role of ORM in the patho-genesis of obesity-associated metabolic derangements.

A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients

Assim A Alfadda,Afshan Masood,Mohammed Y Al-Naami,Pierre Chaurand,Hicham Benabdelkamel 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.9

Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood. In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese pa-tients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p  0.05) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the NFB, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.

Endophilin A2: A Potential Link to Adiposity and Beyond

Assim A Alfadda,Reem M Sallam,Rukhsana Gul,황인재,가소정 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.11

Adipose tissue plays a central role in regulating dynamic crosstalk between tissues and organs. A detailed description of molecules that are differentially expressed upon changes in adipose tissue mass is expected to increase our understanding of the molecular mechanisms that underlie obesity and related metabolic co-morbidities. Our previous studies suggest a possible link between endophilins (SH3Grb2 proteins) and changes in body weight. To explore this further, we sought to assess the distribution of endophilin A2 (EA2) in human adipose tissue and experimental animals. Human paired adipose tissue samples (subcutaneous and visceral) were collected from subjects un-dergoing elective abdominal surgery and abdominal liposuction. We observed elevated EA2 gene expression in the subcutaneous compared to that in the visceral human adipose tissue. EA2 gene expression negatively correlated with adiponectin and chemerin in visceral adipose tissue, and positively correlated with TNF- in subcutaneous adipose tissue. EA2 gene expression was significantly downregulated during differentiation of preadipocytes in vitro. In conclusion, this study provides a description of EA2 distribution and emphasizes a need to study the roles of this protein during the progression of obesity.

Three “DS” - Elements for Successful Weight Loss Outcomes: Role of Healthcare Professionals

( Dror Dicker ),( Assim A Alfadda ),( Pernille Auerbach ),( Ian D Caterson ),( Ada Cuevas ),( Jason Halford ),( Masato Iwabu ),( Jae-Heon Kang ),( Rita Nawar ),( Ricardo Arturo Reynoso Mendoza ),( Nic 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: In people with obesity (PwO), body weight loss of ≥5% is generally considered to be clinically meaningful. Some PwO do receive treatment and guidance from healthcare professionals (HCPs), but there remains a substantial unmet medical outcomes and weight maintenance need. To identify aspects that might contribute to a successful weight loss outcome (WLO; ≥5% body weight loss maintained for ≥1 year), we investigated the characteristics and experience of PwO with and without successful WLOs using data from the ACTION-IO study (NCT03584191). Methods: An online survey was completed by adults with obesity and HCPs in 11 countries: Australia, Chile, Israel, Italy, Japan, Mexico, Saudi Arabia, South Korea, Spain, UAE and UK. A successful WLO was defined as ≥5% body weight loss in the past 3 years maintained for ≥1 year. Results: A total of 14,502 PwO completed the survey. General characteristics were similar between those who had a successful WLO (n=1,559; 11%) vs those who had not (n=12,943; 89%): 53% vs 52% were male; the mean age was 49 vs 48 years; the mean number of comorbidities was 2.0 vs 1.8. The mean number of serious weight loss attempts was 4 for both groups. However, more PwO who had a successful WLO weighed themselves every day (20%) compared with those who had not had a successful WLO (10%). In terms of interactions with HCPs, more PwO who had a successful WLO had discussed weight (58%) with an HCP within the past 5 years than those who did not have a successful WLO (53%). In addition, more PwO who had a successful WLO compared with those who did not had been diagnosed with obesity (42% vs 35%) and had subsequent direction through the scheduling of a follow-up appointment (25% vs 21%). Conclusions: A 3D approach from HCPs (diagnosis, discussion and direction) appears to be a key element in facilitating a successful WLO. Neither gender, nor age, nor number of weight loss attempts was associated with a successful WLO.