William S Blaner

CUNY Graduate Center, New York City, New York, United States

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Publications (202)1040.78 Total impact

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    ABSTRACT: Retinoic acid signaling is required for maintaining a range of cellular processes, including cell differentiation, proliferation, and apoptosis. We investigated the actions of all-trans-retinoic acid (atRA) signaling in pancreatic β-cells of adult mice. atRA signaling was ablated in β-cells by overexpressing a dominant-negative retinoic acid receptor (RAR)-α mutant (RARdn) using an inducible Cre-Lox system under the control of the pancreas duodenal homeobox gene promoter. Our studies establish that hypomorphism for RAR in β-cells leads to an age-dependent decrease in plasma insulin in the fed state and in response to a glucose challenge. Glucose-stimulated insulin secretion was also impaired in islets isolated from mice expressing RARdn. Among genes that are atRA responsive, Glut2 and Gck mRNA levels were decreased in isolated islets from RARdn-expressing mice. Histologic analyses of RARdn-expressing pancreata revealed a decrease in β-cell mass and insulin per β-cell 1 mo after induction of the RARdn. Our results indicate that atRA signaling mediated by RARs is required in the adult pancreas for maintaining both β-cell function and mass, and provide insights into molecular mechanisms underlying these actions.-Brun, P.-J., Grijalva, A., Rausch, R., Watson, E., Yuen, J. J., Das, B. C., Shudo, K., Kagechika, H., Leibel, R. L., Blaner, W. S. Retinoic acid receptor signaling is required to maintain glucose-stimulated insulin secretion and β-cell mass.
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 11/2014;
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    ABSTRACT: Dietary carotenoids like β-carotene are converted within the body either to retinoid, via β-carotene-15,15'-dioxygenase (BCO1), or to β-apo-carotenoids, via β-carotene-9',10'-oxygenase 2 (BCO2). Some β-apo-carotenoids are potent antagonists of retinoic acid receptor (RAR)-mediated transcriptional regulation, which is required to assure normal heart development and functions. We established liquid chromatography tandem mass spectrometery (LC/MS/MS) methods for measuring concentrations of 10 β-apo-carotenoids in mouse plasma, liver and heart and assessed how these are influenced by Bco1-deficiency and β-carotene intake. Surprisingly, Bco1(-/-) mice had an increase in heart levels of retinol, nonesterified fatty acids, and ceramides and a decrease in heart triglycerides. These lipid changes were accompanied by elevations in levels of genes important to retinoid metabolism, specifically Rdh10 and Rbp4, as well as ones involved in lipid metabolism, including Pparg, Lpl, Cd36, Scd1 and Fas. We also obtained evidence of compromised heart function, as assessed by two-dimensional echocardiography, in Bco1(-/-) mice. However, the total absence of Bco1 did not substantially affect β-apo-carotenoid concentrations in heart. β-Carotene administration to matched Bco1-deficient and wild type mice elevated total β-apo-carotenal levels in heart, liver and plasma and total β-apo-carotenoic acid levels in liver. Thus, BCO1 modulates heart metabolism and function possibly by altering levels of cofactors required for the actions of nuclear hormone receptors.
    American journal of physiology. Heart and circulatory physiology. 09/2014;
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    ABSTRACT: Diacylglycerol acyl transferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis, the conversion of diacylglycerol (DAG) to TG. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced Dgat1(-/-) expression associated with accumulation of DAGs and ceramides. To test whether (DGAT1) loss alone affects heart function we created cardiomyocyte specific DGAT1 knockout (hDgat1(-/-)) mice. hDgat1(-/-) mice hearts had 95% increased DAG and 85% increased ceramides compared to floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide (Bnp) increased 5-fold in hDgat1(-/-) hearts and fractional shortening (FS) was reduced. This was associated with increased expression of PPARα and Cd36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knockout mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the GLP-1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activity of protein kinase Cα (PKCα), which is known to be increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.
    Journal of Biological Chemistry 08/2014; · 4.65 Impact Factor
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    ABSTRACT: The hepatic circadian clock plays a pivotal role in regulating major aspects of energy homeostasis and lipid metabolism. In this study, we show that RORγ robustly regulates the rhythmic expression of several lipid metabolic genes, including the insulin-induced gene 2a, Insig2a, elongation of very long chain fatty acids-like 3, Elovl3 and sterol 12α-hydroxylase, Cyp8b1, by enhancing their expression at ZT20-4. The time-dependent increase in their expression correlates with the rhythmic expression pattern of RORγ. The enhanced recruitment of RORγ to ROREs in their promoter region, increased histone acetylation, and reporter and mutation analysis support the concept that RORγ regulates the transcription of several lipid metabolic genes directly by binding ROREs in their promoter regulatory region. Consistent with the disrupted expression of a number of lipid metabolic genes, loss of RORγ reduced the level of several lipids in liver and blood in a ZT-preferred manner. Particularly the whole-body bile acid pool size was considerably reduced in RORγ(-/-) mice in part through its regulation of several Cyp genes. Similar observations were made in liver-specific RORγ-deficient mice. Altogether, our study indicates that RORγ functions as an important link between the circadian clock and the transcriptional regulation of several metabolic genes.
    Nucleic Acids Research 08/2014; · 8.81 Impact Factor
  • Robin D Clugston, William S Blaner
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    ABSTRACT: Vitamin A status is an important consideration in the health of both wild and captive amphibians. Data concerning whole body vitamin A homeostasis in amphibians are scarce, although these animals have been used as experimental models to study the actions of vitamin A in vision, limb regeneration and embryogenesis. The available data suggest that many aspects of vitamin A biology in amphibians are similar to the canonical characteristics of vitamin A metabolism and actions established in mammals. This is consistent with the evolutionary conservation of these important biological processes. Amphibians must obtain vitamin A in their diet, with captive animals being prone to vitamin A deficiency. There is still much to be learned about vitamin A biology in amphibians that can only be achieved through rigorous scientific research. Improved understanding of amphibian vitamin A biology will aid the conservation of endangered amphibians in the wild, as well as the successful maintenance of ex situ populations. Zoo Biol. XX:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
    Zoo Biology 06/2014; · 1.14 Impact Factor
  • Yang Li, Nuttaporn Wongsiriroj, William S Blaner
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    ABSTRACT: Since their discovery over a century ago, retinoids have been the most studied of the fat-soluble vitamins. Unlike most vitamins, retinoids are stored at relatively high concentrations in the body to buffer against nutritional insufficiency. Until recently, it was thought that the sole important retinoid delivery pathway to tissues involved retinol bound to retinol-binding protein (RBP4). More recent findings, however, indicate that retinoids can be delivered to tissues through multiple overlapping delivery pathways, involving chylomicrons, very low density lipoprotein (VLDL) and low density lipoprotein (LDL), retinoic acid bound to albumin, water soluble β-glucuronides of retinol and retinoic acid, and provitamin A carotenoids. This review will focus on explaining this evolving understanding of retinoid metabolism and transport within the body.
    Hepatobiliary surgery and nutrition. 06/2014; 3(3):126-39.
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    ABSTRACT: Background Lipolysis regulates energy homeostasis through the hydrolysis of intracellular triglycerides and the release of fatty acids for use as energy substrates or lipid mediators in cellular processes. Genes encoding proteins that regulate energy homeostasis through lipolysis are thus likely to play an important role in determining susceptibility to metabolic disorders. Methods We sequenced 12 lipolytic-pathway genes in Old Order Amish participants whose fasting serum triglyceride levels were at the extremes of the distribution and identified a novel 19-bp frameshift deletion in exon 9 of LIPE, encoding hormone-sensitive lipase (HSL), a key enzyme for lipolysis. We genotyped the deletion in DNA from 2738 Amish participants and performed association analyses to determine the effects of the deletion on metabolic traits. We also obtained biopsy specimens of abdominal subcutaneous adipose tissue from 2 study participants who were homozygous for the deletion (DD genotype), 10 who were heterozygous (ID genotype), and 7 who were noncarriers (II genotype) for assessment of adipose histologic characteristics, lipolysis, enzyme activity, cytokine release, and messenger RNA (mRNA) and protein levels. Results Carriers of the mutation had dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. In adipose tissue from study participants with the DD genotype, the mutation resulted in the absence of HSL protein, small adipocytes, impaired lipolysis, insulin resistance, and inflammation. Transcription factors responsive to peroxisome-proliferator-activated receptor γ (PPAR-γ) and downstream target genes were down-regulated in adipose tissue from participants with the DD genotype, altering the regulation of pathways influencing adipogenesis, insulin sensitivity, and lipid metabolism. Conclusions These findings indicate the physiological significance of HSL in adipocyte function and the regulation of systemic lipid and glucose homeostasis and underscore the severe metabolic consequences of impaired lipolysis. (Funded by the National Institutes of Health and others).
    New England Journal of Medicine 05/2014; · 54.42 Impact Factor
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    ABSTRACT: Insulin signaling in osteoblasts has been shown recently to contribute to whole-body glucose homeostasis in animals fed a normal diet; however, it is unknown whether bone contributes to the insulin resistance that develops in animals challenged by a high-fat diet (HFD). Here, we evaluated the consequences of osteoblast-specific overexpression of or loss of insulin receptor in HFD-fed mice. We determined that the severity of glucose intolerance and insulin resistance that mice develop when fed a HFD is in part a consequence of osteoblast-dependent insulin resistance. Insulin resistance in osteoblasts led to a decrease in circulating levels of the active form of osteocalcin, thereby decreasing insulin sensitivity in skeletal muscle. Insulin resistance developed in osteoblasts as the result of increased levels of free saturated fatty acids, which promote insulin receptor ubiquitination and subsequent degradation. Together, these results underscore the involvement of bone, among other tissues, in the disruption of whole-body glucose homeostasis resulting from a HFD and the involvement of insulin and osteocalcin cross-talk in glucose intolerance. Furthermore, our data indicate that insulin resistance develops in bone as the result of lipotoxicity-associated loss of insulin receptors.
    The Journal of clinical investigation 03/2014; · 15.39 Impact Factor
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    ABSTRACT: The literature indicates that retinoids can influence the metabolism and actions of xenobiotics and conversely that xenobiotics can influence the metabolism and actions of retinoids. We were interested in understanding the degree to which hepatic retinoid stores, accumulated over a lifetime, affect xenobiotic metabolism and actions. To investigate this, we induced liver injury through administration of the hepatotoxin thioacetamide (TAA) to chow fed wild type (WT) mice and lecithin:retinol acyltransferase-deficient (Lrat(-/-)) mice that are genetically unable to accumulate hepatic retinoid stores. Within 48 h of TAA-treatment, WT mice develop liver injury as evidenced by focal necrotic areas and increases in serum ALT activity and myeloperoxidase activity in hepatic parenchyma. Simultaneously, features of hepatic encephalopathy develop, as evidenced by a 25% increase in blood ammonia and a 3-fold reduction of blood glucose levels. This is accompanied by reduced hepatic glutathione, and increased thiobarbituric acid reactive substances (TBARS), protein carbonyl and sulfhydryl groups, and increased cytochrome P450-catalyzed hydroxylation activity and flavin-containing monooxygenase (FMO) activity in microsomes prepared from WT liver. Strikingly, none of these TAA-induced effects were observed for matched Lrat(-/-) mice. To confirm that TAA hepatotoxicity depends on retinoid availability, we administered, over 48 h, 4 oral doses of 3,000 IU retinyl acetate each to the mice. This led to the development of hepatotoxicity in Lrat(-/-) mice that was similar in extent to that observed in WT mice. Our findings establish that endogenous hepatic retinoid stores can modulate the toxicity of TAA in mice.
    Toxicological Sciences 03/2014; · 4.33 Impact Factor
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    ABSTRACT: CD36 is a scavenger receptor with multiple ligands and cellular functions, including facilitating cellular uptake of free fatty acids (FFA). Chronic alcohol consumption increases hepatic CD36 expression, leading to the hypothesis that this promotes uptake of circulating FFA, which then serve as a substrate for triglyceride (TG) synthesis and the development of alcoholic steatosis. We investigated this hypothesis in alcohol-fed wild-type and Cd36-deficient (Cd36-/-) mice using low-fat/high-carbohydrate Lieber-DeCarli liquid diets, positing that Cd36-/- mice would be resistant to alcoholic steatosis. Our data show that the livers of Cd36-/- mice are resistant to the lipogenic effect of consuming high-carbohydrate liquid diets. These mice also do not further develop alcoholic steatosis when chronically fed alcohol. Surprisingly, we did not detect an effect of alcohol or CD36-deficiency on hepatic FFA uptake; however, the lower baseline levels of hepatic TG in Cd36-/- mice fed a liquid diet were associated with decreased expression of genes in the de novo lipogenesis pathway and a lower rate of hepatic de novo lipogenesis. In conclusion, Cd36-/- mice are resistant to hepatic steatosis when fed a high-carbohydrate liquid diet, and are also resistant to alcoholic steatosis. These studies highlight an important role for CD36 in hepatic lipid homeostasis that is not associated with hepatic fatty acid uptake.
    The Journal of Lipid Research 11/2013; · 4.39 Impact Factor
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    ABSTRACT: Approximately 80-90% of all retinoid in the body is stored as retinyl ester (RE) in liver. Adipose too contributes significantly to RE storage. Employing genetic and nutritional interventions we explored factors that regulate RE accumulation in liver and adipose and how these influence levels of retinoic acid (RA) and RA-responsive gene expression. Our data establish that an acyl-CoA:retinol acyltransferase (ARAT) activity is not involved in RE synthesis in the liver, even when mice are stressed nutritionally upon feeding of a 25-fold excess retinol diet or upon ablation of cellular retinol-binding protein, type I (CRBPI). Unlike liver, where lecithin:retinol acyltransferase (LRAT) is responsible for all RE synthesis, this is not true for adipose where Lrat-deficient mice display elevated RE concentrations. However, when CrbpI is also absent, these resemble wild type levels, suggesting a role for CrbpI in RE accumulation in adipose. Although expression of several RA-responsive genes is elevated in Lrat-deficient liver, employing a sensitive liquid chromatography tandem mass spectrometry protocol, we did not detect elevated concentrations of all-trans-retinoic acid. The elevated RA-responsive gene expression was associated with elevated hepatic triglyceride levels and decreased expression of Pparδ and its Pdk4 target, suggesting a role for RA in these processes in vivo.
    The Journal of Lipid Research 11/2013; · 4.39 Impact Factor
  • William S Blaner
    The Journal of Lipid Research 07/2013; · 4.39 Impact Factor
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    ABSTRACT: The plasma membrane protein STRA6 is thought to mediate uptake of retinol from its blood carrier RBP into cells and to function as a surface receptor which, upon binding of holo-RBP, activates a JAK/STAT cascade. It was suggested that STRA6 signaling underlies insulin resistance induced by elevated serum levels of RBP in obese animals. To investigate these activities in vivo, we generated and analyzed Stra6-null mice. We show that the contribution of STRA6 to retinol uptake by tissues in vivo is small and that, with the exception of the eye, ablation of Stra6 has only a modest effect on retinoid homeostasis and does not impair physiological functions that critically depend on retinoic acid in the embryo or in the adult. However, ablation of Stra6 effectively protects mice from RBP-induced suppression of insulin signaling. One biological function of STRA6 in tissues other than the eye appears therefore to be the coupling of circulating holo-RBP levels to cell signaling, in turn regulating key processes such as insulin response.
    Journal of Biological Chemistry 07/2013; · 4.65 Impact Factor
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    ABSTRACT: Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease.
    Biochimica et Biophysica Acta 07/2013; 1831(7):1276-86. · 4.66 Impact Factor
  • William S Blaner
    The Journal of Lipid Research 05/2013; · 4.39 Impact Factor
  • Sheila M O'Byrne, William S Blaner
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    ABSTRACT: Since the identification of fat soluble A a century ago, retinoids (vitamin A and its natural and synthetic analogs) have been the most extensively studied of the fat soluble vitamins. This research has identified essential roles for retinoids in many different aspects of mammalian physiology including embryonic development, adult growth and development, maintenance of immunity, maintenance of epithelial barriers and vision. This review will focus on retinoid biochemistry in mammals, primarily on retinol and retinyl ester metabolism. However, we also will consider other retinol metabolites including retro- and anhydro-retinoids and retinoid-β-glucuronides.
    The Journal of Lipid Research 04/2013; · 4.39 Impact Factor
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    ABSTRACT: BACKGROUND: -Cardiac dysfunction with sepsis is associated with both inflammation and reduced fatty acid oxidation (FAO). We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction. METHODS AND RESULTS: -E. coli lipopolysaccharide (LPS) administered to C57BL/6 mice (WT) induced cardiac dysfunction and reduced FAO and mRNA levels of peroxisome proliferator-activated receptor (PPAR) α and its downstream targets within 6-8h. Transgenic mice in which cardiomyocyte-specific expression of PPARγ is driven by the alpha myosin heavy chain promoter (αMHC-PPARγ) were protected from LPS-induced cardiac dysfunction. Despite a reduction in PPARα, FAO and associated genes were not decreased in hearts of LPS-treated αMHC-PPARγ mice. LPS treatment, however, continued to induce inflammation-related genes, such as interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor α in hearts of αMHC-PPARγ mice. Treatment of WT mice with LPS and the PPARγ agonist rosiglitazone, but not the PPARα agonist (WY-14643), increased FAO, prevented LPS-mediated reduction of mitochondria and treated cardiac dysfunction, as well as it improved survival despite continued increases in the expression of cardiac inflammatory markers. CONCLUSIONS: -Activation of PPARγ in LPS-treated mice prevented cardiac dysfunction and mortality despite development of cardiac inflammation and PPARα downregulation.
    Circulation Heart Failure 04/2013; · 6.68 Impact Factor
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    ABSTRACT: : Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure either due to transgenic expression of the lipid uptake protein acyl CoA synthetase 1 (ACS1) or overexpression of the transcription factor peroxisomal proliferator-activated receptor (PPAR) γ via the cardiac-specific myosin heavy chain (MHC) promoter. ACS1 mice and control littermates were fed 3 diets containing low-dose or high-dose FO or nonpurified diet (NPD) for 6 weeks. MHC-PPARγ mice were fed low-dose FO or NPD. Compared with control mice fed with NPD, ACS1, and MHC-PPARγ, mice fed with NPD had reduced cardiac function and survival with cardiac fibrosis. In contrast, ACS1 mice fed with high-dose FO had better cardiac function, survival, and less myocardial fibrosis. FO increased eicosapentaenoic and docosahexaenoic acids and reduced saturated fatty acids in cardiac diacylglycerols. This was associated with reduced protein kinase C alpha and beta activation. In contrast, low-dose FO reduced MHC-PPARγ mice survival with no change in protein kinase C activation or cardiac function. Thus, dietary FO reverses fibrosis and improves cardiac function and survival of ACS1 mice but does not benefit all forms of lipid-mediated cardiomyopathy.
    Journal of cardiovascular pharmacology 04/2013; 61(4):345-54. · 2.83 Impact Factor
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    ABSTRACT: Adipose fat storage is thought to require uptake of circulating triglyceride (TG)-derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects the biology of adipose tissue, we created adipose specific LpL knockout (ATLO) mice, and compared them with whole body LpL knockout mice rescued with muscle LpL expression (MCK/L0) and wild type (WT) mice. ATLO LpL mRNA and activity were reduced, respectively, 75% and 70% in gonadal adipose tissue (GAT), 90% and 80% in subcutaneous (SCAT), and 84% and 85% in brown adipose tissue (BAT). ATLO mice had increased plasma TG levels associated with reduced chylomicron TG uptake into BAT and lung. ATLO BAT, but not GAT, had altered TG composition. GAT from MCK/L0 was smaller and contained less polyunsaturated fatty acids in TG, while GAT from ATLO was normal unless LpL was overexpressed in muscle. High fat diet feeding led to less adipose in MCK/L0 mice but TG acyl composition in SCAT and BAT reverted to that of WT. Therefore, adipocyte LpL in BAT modulates plasma lipoprotein clearance and the greater metabolic activity of this depot makes its lipid composition more dependent on LpL-mediated uptake. Loss of adipose LpL reduces fat accumulation only if accompanied by greater LpL activity in muscle. These data support the role of LpL as the gate-keeper for tissue lipid distribution.
    Journal of Biological Chemistry 03/2013; · 4.65 Impact Factor
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    ABSTRACT: Alcohol, a major cause of human cardiomyopathy, decreases cardiac contractility in both animals and man. However, key features of alcohol-related human heart disease are not consistently reproduced in animal models. Accordingly, we studied cardiac histology, contractile function, cardiomyocyte long chain fatty acid (LCFA) uptake, and gene expression in male C57BL/6J mice consuming 0, 10, 14, or 18% ethanol in drinking water for 3months. At sacrifice, all EtOH groups had mildly decreased body and increased heart weights, dose-dependent increases in cardiac triglycerides and a marked increase in cardiac fatty acid ethyl esters. [(3)H]-oleic acid uptake kinetics demonstrated increased facilitated cardiomyocyte LCFA uptake, associated with increased expression of genes encoding the LCFA transporters CD36 and Slc27a1 (FATP1) in EtOH-fed animals. Although SCD-1 expression was increased, lipidomic analysis did not indicate significantly increased de novo LCFA synthesis. By echocardiography, ejection fraction (EF) and the related fractional shortening (FS) of left ventricular diameter during systole were reduced and negatively correlated with cardiac triglycerides. Expression of myocardial PGC-1α and multiple downstream target genes in the oxidative phosphorylation pathway, including several in the electron transport and ATP synthase complexes of the inner mitochondrial membrane, were down-regulated. Cardiac ATP was correspondingly reduced. The data suggest that decreased expression of PGC-1α and its target genes result in decreased cardiac ATP levels, which may explain the decrease in myocardial contractile function caused by chronic EtOH intake. This model recapitulates important features of human alcoholic cardiomyopathy and illustrates a potentially important pathophysiologic link between cardiac lipid metabolism and function.
    Journal of Molecular and Cellular Cardiology 02/2013; · 5.15 Impact Factor

Publication Stats

5k Citations
1,040.78 Total Impact Points


  • 1992–2014
    • CUNY Graduate Center
      New York City, New York, United States
    • State University of New York Downstate Medical Center
      • Department of Pediatrics
      Brooklyn, NY, United States
  • 1982–2014
    • Columbia University
      • • Department of Medicine
      • • Institute of Human Nutrition
      • • College of Physicians and Surgeons
      New York City, New York, United States
  • 2013
    • Yale University
      New Haven, Connecticut, United States
  • 2007–2012
    • Case Western Reserve University
      • Department of Pharmacology
      Cleveland, OH, United States
  • 2008–2011
    • Rutgers, The State University of New Jersey
      • Department of Food Science
      New Brunswick, NJ, United States
  • 2005
    • University of Washington Seattle
      • Department of Ophthalmology
      Seattle, WA, United States
  • 1998
    • Medical College of Wisconsin
      • Department of Physiology
      Milwaukee, WI, United States
  • 1996
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 1988–1990
    • New York Medical College
      • Department of Medicine
      New York City, NY, United States
  • 1989
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 1980
    • The University of Tennessee Medical Center at Knoxville
      Knoxville, Tennessee, United States