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Full-Text Articles in Life Sciences
Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun
Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun
Department of Biochemistry: Faculty Publications
Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …
Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon
Genetic Engineering Of Lesquerella With Increased Ricinoleic Acid Content In Seed Oil, Grace Q. Chen, Kumiko Johnson, Tara J. Nazarenus, Grisel Ponciano, Eva Morales, Edgar B. Cahoon
Department of Biochemistry: Faculty Publications
Seeds of castor (Ricinus communis) are enriched in oil with high levels of the industrially valuable fatty acid ricinoleic acid (18:1OH), but production of this plant is limited because of the cooccurrence of the ricin toxin in its seeds. Lesquerella (Physaria fendleri) is being developed as an alternative industrial oilseed because its seeds accumulate lesquerolic acid (20:1OH), an elongated form of 18:1OH in seed oil which lacks toxins. Synthesis of 20:1OH is through elongation of 18:1OH by a lesquerella elongase, PfKCS18. Oleic acid (18:1) is the substrate for 18:1OH synthesis, but it is also used by fatty acid desaturase 2 …
Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun
Long Non-Coding Rna Meg3 Deficiency Impairs Glucose Homeostasis And Insulin Signaling By Inducing Cellular Senescence Of Hepatic Endothelium In Obesity, Xiao Cheng, Mohamed Sham Shihabudeen Haider Ali, Matthew Moran, Martonio Ponte Viana, Sarah L. Schlichte, Matthew C. Zimmerman, Oleh Khalimonchuk, Mark W. Feinberg, Xinghui Sun
Department of Biochemistry: Faculty Publications
Obesity-induced insulin resistance is a risk factor for diabetes and cardiovascular disease. However, the mechanisms underlying endothelial senescence in obesity, and how it impacts obesity-induced insulin resistance remain incompletely understood. In this study, transcriptome analysis revealed that the long non-coding RNA (lncRNA) Maternally expressed gene 3 (Meg3) is one of the top differentially expressed lncRNAs in the vascular endothelium in diet-induced obese mice. Meg3 knockdown induces cellular senescence of endothelial cells characterized by increased senescence-associated β–galactosidase activity, increased levels of endogenous superoxide, impaired mitochondrial structure and function, and impaired autophagy. Moreover, Meg3 knockdown causes cellular senescence of hepatic endothelium in …
Genomic And Proteomic Effects Of Red Raspberry (Rubus Idaeus) Consumption On The Perivascular Adipose Tissue Of The Obese Zucker Rat, A Model Of Human Metabolic Syndrome, Jasmine Waite
Honors College
The Metabolic Syndrome (MetS) affects 35% of U.S. adults and is an indicator of early death. While pharmacological treatments have been developed for the majority of MetS risk factors, obesity-induced inflammation remains to be addressed. Dysfunctional adipose tissue is a source of inflammation, and perivascular adipose tissue (PVAT) is critical in its pathogenesis. This study investigates the effects of red raspberry (rubus idaeus) diet-enrichment on inflammation of PVAT. The obese Zucker rat (OZR) model of MetS and the lean Zucker rat (LZR) control (C) model were used. Rats received an eight-week control or whole red raspberry-enriched (WRR) diet …
Autophagy In Adipocyte Browning: Emerging Drug Target For Intervention In Obesity, Seung-Hyun Ro, Yura Jang, Jiyoung Bae, Isaac M. Kim, Cameron Schaecher, Zachery D. Shomo
Autophagy In Adipocyte Browning: Emerging Drug Target For Intervention In Obesity, Seung-Hyun Ro, Yura Jang, Jiyoung Bae, Isaac M. Kim, Cameron Schaecher, Zachery D. Shomo
Department of Biochemistry: Faculty Publications
Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted …
Blockade Of Cb1 Cannabinoid Receptor Alters Gut Microbiota And Attenuates Inflammation And Diet-Induced Obesity, Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S. Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly Enos, Kandy T. Velazquez, Jamie Mccellan, Mitzi Nagarkatti, Prakash Nagarkatti
Blockade Of Cb1 Cannabinoid Receptor Alters Gut Microbiota And Attenuates Inflammation And Diet-Induced Obesity, Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S. Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly Enos, Kandy T. Velazquez, Jamie Mccellan, Mitzi Nagarkatti, Prakash Nagarkatti
Faculty Publications
Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines …
Interleukin-18 Polymorphism As An Inflammatory Index In Metabolic Syndrome: A Preliminary Study, Syeda Sadia Fatima, Zehra Jamil, Syed Hani Abidi, Daniyal Nadeem, Zara Bashir, Ahmed Ansari
Interleukin-18 Polymorphism As An Inflammatory Index In Metabolic Syndrome: A Preliminary Study, Syeda Sadia Fatima, Zehra Jamil, Syed Hani Abidi, Daniyal Nadeem, Zara Bashir, Ahmed Ansari
Department of Biological & Biomedical Sciences
Aim: To assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes.
Methods: This study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m2), overweight (23.0-25.9 kg/m2) and obese (> 26.0 kg/m2) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)alpha were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance …
C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm
C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm
Molecular and Cellular Biochemistry Faculty Publications
C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …
Gestational Diabetes Mellitus And The Predisposing Factors, Syeda Sadia Fatima, Rehana Rehman, Faiza Alam, Sarosh Madhani, Bushra Chaudhry, Taseer Ahmed Khan
Gestational Diabetes Mellitus And The Predisposing Factors, Syeda Sadia Fatima, Rehana Rehman, Faiza Alam, Sarosh Madhani, Bushra Chaudhry, Taseer Ahmed Khan
Department of Biological & Biomedical Sciences
Objective: To evaluate the occurrence of gestational diabetes mellitus and its association with demographic and anthropometric variables in pregnant women.
Methods: This cross-sectional study was conducted at the Aga Khan University Hospital, Abbasi Shaheed Hospital and Memon Hospital in Karachi, from February 2014 to December 2015, and comprised pregnant women who were screened by 75-g 2-hour oral glucose tolerance test, (24-28 weeks of gestation) and classified as per the criteria of the International Association of Diabetes and Pregnancy Study Group. Weight, body mass index and serum glycated haemoglobin levels were measured. Women with pre-gestational diabetes were excluded. SPSS 21 was …
Suppression Of Nlrp3 Inflammasome By Γ-Tocotrienol Ameliorates Type 2 Diabetes, Yongeun Kim, Wei Wang, Meshail Okla, Inhae Kang, Regis Moreau, Soonkyu Chung
Suppression Of Nlrp3 Inflammasome By Γ-Tocotrienol Ameliorates Type 2 Diabetes, Yongeun Kim, Wei Wang, Meshail Okla, Inhae Kang, Regis Moreau, Soonkyu Chung
Department of Nutrition and Health Sciences: Faculty Publications
The Nod-like receptor 3 (NLRP3) inflammasome is an intracellular sensor that sets off the innate immune system in response to microbial-derived and endogenous metabolic danger signals. We previously reported that γ-tocotrienol (γT3) attenuated adipose tissue inflammation and insulin resistance in diet-induced obesity, but the underlying mechanism remained elusive. Here, we investigated the effects of γT3 on NLRP3 inflammasome activation and attendant consequences on type 2 diabetes. γT3 repressed inflammasome activation, caspase-1 cleavage, and interleukin (IL) 1β secretion in murine macrophages, implicating the inhibition of NLRP3 inflammasome in the anti-inflammatory and antipyroptotic properties of γT3. Furthermore, supplementation of leptin-receptor KO mice …
Effect Of Raised Body Fat On Vitamin D, Leptin And Bone Mass, Syeda Sadia Fatima, Saad Farooq, Maaida Asif Tauni, Omar Irfan, Faiza Alam
Effect Of Raised Body Fat On Vitamin D, Leptin And Bone Mass, Syeda Sadia Fatima, Saad Farooq, Maaida Asif Tauni, Omar Irfan, Faiza Alam
Department of Biological & Biomedical Sciences
Objective: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation.Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C ( > 28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and …
Prevalence Of Obesity And Overweight, Its Clinical Markers And Associated Factors In A High Risk South-Asian Population, Faridah Amin, Syeda Sadia Fatima, Najmul Islam, Anwar H. Gilani
Prevalence Of Obesity And Overweight, Its Clinical Markers And Associated Factors In A High Risk South-Asian Population, Faridah Amin, Syeda Sadia Fatima, Najmul Islam, Anwar H. Gilani
Department of Biological & Biomedical Sciences
Background: Obesity is a global epidemic, which is a risk factor for cardiovascular diseases and metabolic abnormalities. It is measured by body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), body fat (BF) distribution and abdominal fat mass, each having its own merits and limitations. Variability in body composition between ethnic groups in South-Asians is significant and may not be truly reflected by BMI alone, which may result in misclassification. This study therefore, aims to determine the frequency of obesity, body fat composition and distribution, in a high risk population of an urban slum of Karachi, Pakistan. This survey …
Increased Body Mass Index May Lead To Hyperferritinemia Irrespective Of Body Iron Stores, Faiza Alam, Abdul Shakoor Memon, Syeda Sadia Fatima
Increased Body Mass Index May Lead To Hyperferritinemia Irrespective Of Body Iron Stores, Faiza Alam, Abdul Shakoor Memon, Syeda Sadia Fatima
Department of Biological & Biomedical Sciences
Objective: Obesity causes subclinical inflammation which results in the secretion of various bioactive peptides that are key players in metabolic regulation of iron homeostasis. We sought to establish correlation of one such peptide (ferritin) with marker of subclinical inflammation (CRP) in various BMI.
Methods: Total 150 subjects between the ages of 20-60 years were included in the cross-sectional study conducted at Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, Pakistan. Body Mass Index (BMI) was calculated by weight (kg) /height (m(2)). The given values were used as reference for Group A: normal weight (18.0-22.9 kg/m2), Group B: overweight …
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
Coprinus Comatus Cap Inhibits Adipocyte Differentiation Via Regulation Of Pparγ And Akt Signaling Pathway, Hyoung Joon Park, Jisoo Yun, Hong-Duck Kim, Chung-Kil Won, Gon-Sup Kim, Jae-Hyeon Cho
NYMC Faculty Publications
This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the …
Molecular Characterization Of A Patient Presumed To Have Prader-Willi Syndrome, Marina Falaleeva, Carlos R. Sulsona, Horst R. Zielke, Kathleen M. Currey, Pierre De La Grange, Vahid Aslanzadeh, Daniel J. Driscoll, Stefan Stamm
Molecular Characterization Of A Patient Presumed To Have Prader-Willi Syndrome, Marina Falaleeva, Carlos R. Sulsona, Horst R. Zielke, Kathleen M. Currey, Pierre De La Grange, Vahid Aslanzadeh, Daniel J. Driscoll, Stefan Stamm
Molecular and Cellular Biochemistry Faculty Publications
Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. Currently, there are no mouse models that faithfully reflect the human phenotype and investigations rely on human post-mortem material. During molecular characterization of tissue deposited in a public brain bank from a patient diagnosed with Prader-Willi syndrome, we found RNA expression from SNRPN, SNORD115, and SNORD116 which does not support a genetic diagnosis of Prader-Willi syndrome. The patient was a female, Caucasian nursing home resident with history of morbid obesity (BMI 56.3) and mental retardation. She …
Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott
Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott
Department of Biochemistry: Faculty Publications
MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.