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1.
Surg Obes Relat Dis ; 20(6): 527-531, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38195313

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days. OBJECTIVES: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis. SETTING: University Hospital. METHODS: Between 2012-2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018-2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed. RESULTS: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m2, respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively. CONCLUSIONS: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively.


Subject(s)
Chemoprevention , Gastrectomy , Laparoscopy , Portal Vein , Postoperative Complications , Venous Thrombosis , Humans , Female , Male , Gastrectomy/adverse effects , Gastrectomy/methods , Adult , Middle Aged , Laparoscopy/adverse effects , Venous Thrombosis/prevention & control , Venous Thrombosis/etiology , Chemoprevention/methods , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Mesenteric Veins , Rivaroxaban/administration & dosage , Obesity, Morbid/surgery , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Retrospective Studies , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Postoperative Hemorrhage/prevention & control , Postoperative Hemorrhage/etiology
2.
Am Surg ; 89(6): 2554-2562, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35599614

ABSTRACT

BACKGROUND: Acute appendicitis (AA) is the most common surgical emergency, with a relatively stable yearly incidence. During the first wave of the COVID-19 pandemic, as New York City (NYC) emerged as the US epicenter, hospitals saw a marked reduction in patients presenting with non-COVID-related diseases. The objective of this study was to characterize the effects of the pandemic on the incidence, presentation, and management of AA. METHODS: A retrospective analysis of patients with AA who presented to two academic medical centers during the NYC COVID peak (March 22nd-May 31st, 2020) was performed. This group was compared to a control cohort presenting during the same period in 2019. Primary outcomes included the incidence of AA, complicated disease, and management. Secondary outcomes included duration of symptoms, hospital length of stay, and complication rates. Statistical analyses were performed using Mann-Whitney U, Chi-square, and Fisher's exact tests. RESULTS: A 49.1% reduction in the incidence of AA was seen between 2019 (n = 114) and 2020 (n = 58). Median duration of symptoms doubled from 1 day in 2019 to 2 days in 2020 (P < .02). Proportionally, the incidence of complicated appendicitis rose from 19.3% to 41.4% (P < .005). 32.4% of patients with uncomplicated AA underwent non-operative management in 2020, compared to 12% in 2019 (P < .02). Hospital length of stay and complication rates were similar between years. DISCUSSION: Significantly fewer AA patients presented during the initial phase of the pandemic. Patients presented later, which may have contributed to a higher proportion of complicated disease. Surgeons were also more likely to treat uncomplicated AA nonoperatively than they were prior. Further research is needed to understand the long-term consequences of these changes.


Subject(s)
Appendicitis , COVID-19 , Humans , COVID-19/epidemiology , COVID-19/complications , Pandemics , Appendicitis/epidemiology , Appendicitis/surgery , Retrospective Studies , Appendectomy , Acute Disease
3.
Surg Obes Relat Dis ; 16(7): 839-843, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32312684

ABSTRACT

BACKGROUND: Portomesenteric vein thrombosis (PMVT) may occur after laparoscopic sleeve gastrectomy (LSG). Previous studies have shown that PMVT patients may have undiagnosed thrombophilia. We recently changed our practice to check thrombophilia panel in every LSG patient preoperatively. OBJECTIVES: To estimate the thrombophilia prevalence in patients seeking LSG, and determine if extended chemoprophylaxis post LSG reduces PMVT. SETTINGS: University hospital. METHODS: Thrombophilia panels were drawn on every patient seeking LSG after July 2018 at 2 high-volume accredited bariatric surgery centers. A positive panel included factor VIII >150%; protein C <70%; protein S <55%; antithrombin III <83%; and activated protein C resistance <2.13. Patients with a positive panel were discharged on extended chemoprophylaxis. PMVT rates and bleeding occurrences were recorded for LSG patients from August 2018 to March 2019 and were compared with a historic cohort of LSG performed from January 2014 to July 2018. RESULTS: One thousand seventy-five patients seeking LSG had thrombophilia panel checked preoperatively. The cohort was 83% female; mean age and body mass index were 39.2 years and 43 kg/m2, respectively. Of the cohort, 52.4% (563/1075) had positive thrombophilia panel, including factor VIII elevation (91.5%), antithrombin III deficiency (6.0%), protein S deficiency (1.1%), protein C deficiency (.9%), and activated protein C resistance (.5%). Between January 2014 and July 2018, 13 PMVT were diagnosed among 4228 LSG (.3%) and there were 17 bleeding occurrences (.4%). After August 2018, one PMVT was diagnosed among 745 LSG (.1%) and there were 5 bleeding occurrences (.6%). CONCLUSIONS: The estimated thrombophilia prevalence in patients seeking LSG is 52.4%. The majority (91.5%) of these patients have factor VIII elevation. Extended prophylaxis may decrease PMVT postLSG.


Subject(s)
Laparoscopy , Obesity, Morbid , Thrombophilia , Chemoprevention , Female , Gastrectomy/adverse effects , Humans , Male , Mesenteric Veins , Obesity, Morbid/surgery , Portal Vein , Prevalence , Retrospective Studies , Thrombophilia/epidemiology
4.
Surg Obes Relat Dis ; 13(11): 1835-1839, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28964696

ABSTRACT

BACKGROUND: Portomesenteric vein thrombosis (PMVT) has been increasingly reported after laparoscopic sleeve gastrectomy (LSG). Factor VIII (FVIII) is a plasma sialoglycoprotein that plays an essential role in hemostasis. There is increasing evidence that FVIII elevation constitutes a clinically important risk factor for venous thrombosis. OBJECTIVES: To report the prevalence of FVIII elevation as well as other clinical characteristics in a multicenter series of patients who developed PMVT after LSG. SETTING: University hospitals. METHODS: A retrospective review was conducted of all patients that developed PMVT after laparoscopic bariatric surgery from 2006 to 2016 at 6 high-volume bariatric surgery centers. RESULTS: Forty patients who developed PMVT postoperatively, all after LSG, were identified. During this timeframe, 25,569 laparoscopic bariatric surgery cases were performed, including 9749 LSG (PMVT incidence after LSG = .4%). Mean age and body mass index were 40 years (18-65) and 43.4 kg/m2 (35-59.7), respectively. Abdominal pain was the most common (98%) presenting symptom. Of patients, 92% had a hematologic abnormality identified, and of these, FVIII elevation was the most common (76%). The vast majority (90%) was successfully managed with therapeutic anticoagulation alone. A smaller number of patients required small bowel resection (n = 2) and surgical thrombectomy (n = 1). There were no mortalities. CONCLUSIONS: A high index of clinical suspicion and prompt diagnosis/treatment of PMVT usually leads to favorable outcomes. FVIII elevation was the most common (76%) hematologic abnormality identified in this patient cohort. Further studies are needed to determine the prevalence of FVIII elevation in patients seeking bariatric surgery.


Subject(s)
Factor VIII/metabolism , Gastrectomy/adverse effects , Laparoscopy/adverse effects , Mesenteric Ischemia/etiology , Mesenteric Veins , Obesity, Morbid/surgery , Venous Thrombosis/blood , Adolescent , Adult , Aged , Biomarkers/blood , Female , Fibrinolytic Agents/therapeutic use , Humans , Incidence , Male , Mesenteric Ischemia/blood , Mesenteric Ischemia/drug therapy , Middle Aged , Retrospective Studies , Thrombolytic Therapy/methods , United States/epidemiology , Venous Thrombosis/complications , Venous Thrombosis/epidemiology , Young Adult
5.
Surg Obes Relat Dis ; 13(11): 1899-1905, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28797671

ABSTRACT

BACKGROUND: At our medical center, female patients who have undergone bariatric surgery are advised to defer pregnancy for 2 years after surgery to avoid the following complications and their potential consequences for the fetus: inadequate gestational weight gain, inadequate postsurgical weight loss, hyperemesis gravidarum, nutritional deficiencies, gestational diabetes, and gestational hypertension. OBJECTIVES: To examine the effect of time from surgery to conception on pregnancy course and outcomes in bariatric patients. SETTING: University. METHODS: We identified 73 pregnancies in 54 women who became pregnant after undergoing bariatric surgery. Surgery to conception interval was compared between pregnancies that were carried to delivery and 8 pregnancies that resulted in spontaneous abortion. Of 41 pregnancies that were carried to delivery, 26 occurred in women who had undergone surgery less than 2 years before conception, and 15 occurred in women who had undergone surgery greater than 2 years before conception. Gestational age at delivery, number of neonatal intensive care unit admissions, gestational weight gain, hyperemesis gravidarum, nutritional deficiencies, gestational diabetes, and gestational hypertension during pregnancy were compared for the 2 groups. RESULTS: Eight patients who had spontaneous abortion had a significantly shorter time from surgery to conception. There were no significant differences between our 2 groups in rates of preterm deliveries, neonatal intensive care unit admission, gestational weight gain, hyperemesis, nutritional deficiencies, gestational diabetes, or gestational hypertension. CONCLUSIONS: Becoming pregnant within the first 2 years after bariatric surgery appears to have no effect on pregnancy course and outcomes. Women who miscarried had a significantly lower mean surgery to conception interval. These results fail to show an increased rate of pregnancy complications during the first 2 years after bariatric surgery.


Subject(s)
Bariatric Surgery/methods , Fertility/physiology , Fertilization/physiology , Obesity, Morbid/surgery , Pregnancy Outcome , Time-to-Pregnancy/physiology , Adult , Female , Follow-Up Studies , Humans , Infant, Newborn , Pregnancy
7.
Gastroenterology ; 147(5): 1073-83.e6, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25083607

ABSTRACT

BACKGROUND & AIMS: Nonalcoholic fatty liver disease is a common consequence of human and rodent obesity. Disruptions in lipid metabolism lead to accumulation of triglycerides and fatty acids, which can promote inflammation and fibrosis and lead to nonalcoholic steatohepatitis. Circulating levels of fibroblast growth factor (FGF)21 increase in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis; therefore, we assessed the role of FGF21 in the progression of murine fatty liver disease, independent of obesity, caused by methionine and choline deficiency. METHODS: C57BL/6 wild-type and FGF21-knockout (FGF21-KO) mice were placed on methionine- and choline-deficient (MCD), high-fat, or control diets for 8-16 weeks. Mice were weighed, and serum and liver tissues were collected and analyzed for histology, levels of malondialdehyde and liver enzymes, gene expression, and lipid content. RESULTS: The MCD diet increased hepatic levels of FGF21 messenger RNA more than 50-fold and serum levels 16-fold, compared with the control diet. FGF21-KO mice had more severe steatosis, fibrosis, inflammation, and peroxidative damage than wild-type C57BL/6 mice. FGF21-KO mice had reduced hepatic fatty acid activation and ß-oxidation, resulting in increased levels of free fatty acid. FGF21-KO mice given continuous subcutaneous infusions of FGF21 for 4 weeks while on an MCD diet had reduced steatosis and peroxidative damage, compared with mice not receiving FGF21. The expression of genes that regulate inflammation and fibrosis were reduced in FGF21-KO mice given FGF21, similar to those of wild-type mice. CONCLUSIONS: FGF21 regulates fatty acid activation and oxidation in livers of mice. In the absence of FGF21, accumulation of inactivated fatty acids results in lipotoxic damage and increased steatosis.


Subject(s)
Choline Deficiency/complications , Fatty Acids/metabolism , Fibroblast Growth Factors/metabolism , Liver/metabolism , Methionine/deficiency , Non-alcoholic Fatty Liver Disease/prevention & control , Animals , Disease Models, Animal , Disease Progression , Fibroblast Growth Factors/administration & dosage , Fibroblast Growth Factors/blood , Fibroblast Growth Factors/deficiency , Fibroblast Growth Factors/genetics , Hepatitis/genetics , Hepatitis/metabolism , Hepatitis/prevention & control , Inflammation Mediators/metabolism , Infusions, Subcutaneous , Lipid Peroxidation/drug effects , Liver/pathology , Liver Cirrhosis/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/prevention & control , Mice, Inbred C57BL , Mice, Knockout , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/pathology , Oxidation-Reduction , RNA, Messenger/metabolism , Recombinant Proteins/administration & dosage , Severity of Illness Index , Time Factors
8.
Diabetes ; 60(3): 757-65, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21282370

ABSTRACT

OBJECTIVE: Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS: PTRF expression was examined in different adipose depots of mice during fasting, refeeding, and after administration of catecholamines and insulin. Involvement of PTRF during lipolysis was studied upon PTRF knockdown and overexpression and mutation of PTRF phosphorylation sites in 3T3-L1 adipocytes. RESULTS: PTRF expression in mouse white adipose tissue (WAT) is regulated by nutritional status, increasing during fasting and decreasing to baseline after refeeding. Expression of PTRF also is hormonally regulated because treatment of mice with insulin leads to a decrease in expression, whereas isoproterenol increases expression in WAT. Manipulation of PTRF levels revealed a role of PTRF in lipolysis. Lentiviral-mediated knockdown of PTRF resulted in a marked attenuation of glycerol release in response to isoproterenol. Conversely, overexpressing PTRF enhanced isoproterenol-stimulated glycerol release. Mass-spectrometric analysis revealed that PTRF is phosphorylated at multiple sites in WAT. Mutation of serine 42, threonine 304, or serine 368 to alanine reduced isoproterenol-stimulated glycerol release in 3T3-L1 adipocytes. CONCLUSIONS: Our study is the first direct demonstration for a novel adipose tissue-specific function of PTRF as a mediator of lipolysis and also shows that phosphorylation of PTRF is required for efficient fat mobilization.


Subject(s)
Adipocytes/metabolism , Adipose Tissue/metabolism , Lipolysis/physiology , RNA-Binding Proteins/metabolism , 3T3 Cells , Adipocytes/cytology , Adipocytes/drug effects , Adipose Tissue/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , Blotting, Western , Cells, Cultured , Chromatography, Liquid , Insulin/pharmacology , Isoproterenol/pharmacology , Lipolysis/drug effects , Membrane Proteins , Mice , Organ Specificity , Phosphorylation/drug effects , Phosphorylation/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering , RNA-Binding Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tandem Mass Spectrometry
9.
Diabetes ; 59(11): 2781-9, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20682689

ABSTRACT

OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a key mediator of fatty acid oxidation and lipid metabolism. Pharmacological doses of FGF21 improve glucose tolerance, lower serum free fatty acids, and lead to weight loss in obese mice. Surprisingly, however, FGF21 levels are elevated in obese ob/ob and db/db mice and correlate positively with BMI in humans. However, the expected beneficial effects of endogenous FGF21 to increase glucose tolerance and reduce circulating triglycerides are absent in obesity. RESEARCH DESIGN AND METHODS: To test the hypothesis that obesity is a state of FGF21 resistance, we evaluated the response of obese mice to exogenous FGF21 administration. In doing this, we assessed the impact of diet-induced obesity on FGF21 signaling and resultant transcriptional events in the liver and white adipose tissue. We also analyzed the physiologic impact of FGF21 resistance by assessing serum parameters that are acutely regulated by FGF21. RESULTS: When obese mice are treated with FGF21, they display both a significantly attenuated signaling response as assessed by extracellular mitogen-activated protein kinase 1 and 2 (ERK1/2) phosphorylation as well as an impaired induction of FGF21 target genes, including cFos and EGR1. These effects were seen in both liver and fat. Similarly, changes in serum parameters such as the decline in glucose and free fatty acids are attenuated in FGF21-treated DIO mice. CONCLUSIONS: These data demonstrate that DIO mice have increased endogenous levels of FGF21 and respond poorly to exogenous FGF21. We therefore propose that obesity is an FGF21-resistant state.


Subject(s)
Fibroblast Growth Factors/pharmacology , Obesity/blood , Adipose Tissue/drug effects , Adipose Tissue/physiology , Animals , Drug Resistance , Fibroblast Growth Factors/administration & dosage , Fibroblast Growth Factors/blood , Fibroblast Growth Factors/physiology , Humans , Injections, Intravenous , Liver/drug effects , Liver/physiology , Mice , Mice, Inbred C57BL , Mice, Obese , Mitogen-Activated Protein Kinase 3/metabolism , RNA, Messenger/blood , RNA, Messenger/drug effects , RNA, Messenger/genetics , Recombinant Proteins/blood , Recombinant Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/physiology
10.
Gastroenterology ; 139(2): 456-63, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20451522

ABSTRACT

BACKGROUND & AIMS: Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH. RESULTS: There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased. CONCLUSIONS: FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.


Subject(s)
Fatty Liver/blood , Fibroblast Growth Factors/blood , Liver/metabolism , Nutritional Status , Obesity/blood , Adipose Tissue, White/metabolism , Adult , Biomarkers/blood , Body Mass Index , Diet, Ketogenic , Fasting/blood , Fatty Liver/genetics , Fatty Liver/physiopathology , Female , Fibroblast Growth Factors/genetics , Humans , Male , Obesity/physiopathology , Prospective Studies , RNA, Messenger/metabolism , Time Factors , Up-Regulation , Young Adult
11.
J Clin Invest ; 115(8): 2244-56, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16007265

ABSTRACT

In addition to its role in energy storage, adipose tissue also accumulates cholesterol. Concentrations of cholesterol and triglycerides are strongly correlated in the adipocyte, but little is known about mechanisms regulating cholesterol metabolism in fat cells. Here we report that antidiabetic thiazolidinediones (TZDs) and other ligands for the nuclear receptor PPARgamma dramatically upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by facilitating the exchange of coactivators for corepressors on the OLR1 gene in cultured mouse adipocytes. TZDs markedly stimulate the uptake of oxidized LDL (oxLDL) into adipocytes, and this requires OLR1. Increased OLR1 expression, resulting either from TZD treatment or adenoviral gene delivery, significantly augments adipocyte cholesterol content and enhances fatty acid uptake. OLR1 expression in white adipose tissue is increased in obesity and is further induced by PPARgamma ligand treatment in vivo. Serum oxLDL levels are decreased in both lean and obese diabetic animals treated with TZDs. These data identify OLR1 as a novel PPARgamma target gene in adipocytes. While the physiological role of adipose tissue in cholesterol and oxLDL metabolism remains to be established, the induction of OLR1 is a potential means by which PPARgamma ligands regulate lipid metabolism and insulin sensitivity in adipocytes.


Subject(s)
Adipocytes/metabolism , Cholesterol/metabolism , PPAR gamma/metabolism , Receptors, LDL/biosynthesis , Animals , Cells, Cultured , Fatty Acids/metabolism , Gene Expression Regulation/drug effects , Hypoglycemic Agents/pharmacology , Insulin Resistance , Lipoproteins, LDL/metabolism , Mice , Receptors, Oxidized LDL , Scavenger Receptors, Class E , Thiazolidinediones/pharmacology
12.
Genes Dev ; 19(4): 453-61, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15681609

ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPARgamma) is the master regulator of adipogenesis as well as the target of thiazolidinedione (TZD) antidiabetic drugs. Many PPARgamma target genes are induced during adipogenesis, but others, such as glycerol kinase (GyK), are expressed at low levels in adipocytes and dramatically up-regulated by TZDs. Here, we have explored the mechanism whereby an exogenous PPARgamma ligand is selectively required for adipocyte gene expression. The GyK gene contains a functional PPARgamma-response element to which endogenous PPARgamma is recruited in adipocytes. However, unlike the classic PPARgamma-target gene aP2, which is constitutively associated with coactivators, the GyK gene is targeted by nuclear receptor corepressors in adipocytes. TZDs trigger the dismissal of corepressor histone deacetylase (HDAC) complexes and the recruitment of coactivators to the GyK gene. TZDs also induce PPARgamma-Coactivator 1alpha (PGC-1alpha), whose recruitment to the GyK gene is sufficient to release the corepressors. Thus, selective modulation of adipocyte PPARgamma target genes by TZDs involves the dissociation of corepressors by direct and indirect mechanisms.


Subject(s)
Adipocytes/physiology , PPAR gamma/physiology , Repressor Proteins/physiology , Transcription, Genetic/physiology , 3T3-L1 Cells , Adipocytes/enzymology , Animals , Base Sequence , DNA Primers , Glycerol Kinase/genetics , Glycerol Kinase/metabolism , Mice , Molecular Sequence Data , PPAR gamma/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Protein Binding , Sequence Homology, Nucleic Acid , Thiazolidinediones/pharmacology , Trans-Activators/biosynthesis , Transcription Factors , Transcription, Genetic/drug effects
13.
J Clin Invest ; 114(9): 1281-9, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15520860

ABSTRACT

Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of approximately 50% of gene transcripts encoding mitochondrial proteins were decreased with the onset of obesity. About half of those genes were upregulated after treatment with rosiglitazone, and this was accompanied by an increase in mitochondrial mass and changes in mitochondrial structure. Functionally, adipocytes from rosiglitazone-treated mice displayed markedly enhanced oxygen consumption and significantly increased palmitate oxidation. These data reveal mitochondrial remodeling and increased energy expenditure in white fat in response to rosiglitazone treatment in vivo and suggest that enhanced lipid utilization in this tissue may affect whole-body energy homeostasis and insulin sensitivity.


Subject(s)
Adipose Tissue/pathology , Mitochondria/pathology , Thiazolidinediones/pharmacology , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/metabolism , Adipocytes/pathology , Animals , Blood Glucose/metabolism , Blotting, Northern , Blotting, Western , Chaperonin 60/metabolism , Fatty Acids/metabolism , Insulin/metabolism , Mass Spectrometry , Mice , Mice, Inbred C57BL , Mice, Obese , Mice, Transgenic , Microscopy, Fluorescence , Mitochondria/metabolism , Obesity , Oligonucleotide Array Sequence Analysis , Oxygen/metabolism , PPAR gamma/metabolism , Palmitic Acid/chemistry , RNA, Complementary/metabolism , RNA, Messenger/metabolism , Rosiglitazone , Time Factors , Vasodilator Agents/pharmacology
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