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Article ; Online: Is there evidence to support use of premixed or prandial insulin regimens in insulin-naive or previously insulin-treated type 2 diabetic patients?

Yki-Järvinen, Hannele / Kotronen, Anna

2013 Volume 36 Suppl 2, Page(s) S205–11

MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents/administration & dosage ; Insulin/administration & dosage ; Treatment Outcome
Chemical Substances	Hypoglycemic Agents ; Insulin
Language	English
Publishing date	2013-07-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dcS13-2026
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Fatty liver: a novel component of the metabolic syndrome.

Kotronen, Anna / Yki-Järvinen, Hannele

Arteriosclerosis, thrombosis, and vascular biology

2008 Volume 28, Issue 1, Page(s) 27–38

Abstract: Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals ... ...

Abstract	Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD) by gastroenterologists. The fatty liver is insulin resistant. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome independent of obesity. Overproduction of glucose, VLDL, CRP, and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease associated with the metabolic syndrome and NAFLD. Both of the latter conditions also increase the risk of type 2 diabetes and advanced liver disease. The reason why some deposit fat in the liver whereas others do not is poorly understood. Individuals with a fatty liver are more likely to have excess intraabdominal fat and inflammatory changes in adipose tissue. Intervention studies have shown that liver fat can be decreased by weight loss, PPARgamma agonists, and insulin therapy.
MeSH term(s)	Diabetes Mellitus, Type 2/physiopathology ; Fatty Liver/complications ; Fatty Liver/physiopathology ; Female ; Humans ; Insulin Resistance/physiology ; Male ; Metabolic Syndrome/complications ; Metabolic Syndrome/physiopathology ; Waist-Hip Ratio/adverse effects
Language	English
Publishing date	2008-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.107.147538
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Article ; Online: Unravelling the pathogenesis of fatty liver disease: patatin-like phospholipase domain-containing 3 protein.

Romeo, Stefano / Huang-Doran, Isabel / Baroni, Marco Giorgio / Kotronen, Anna

Current opinion in lipidology

2010 Volume 21, Issue 3, Page(s) 247–252

Abstract: Purpose of review: Hepatic steatosis is a leading cause of adult and paediatric liver disease and is inextricably linked to obesity, insulin resistance and cardiovascular disease. Here we summarize our current understanding of the role of the patatin- ... ...

Abstract	Purpose of review: Hepatic steatosis is a leading cause of adult and paediatric liver disease and is inextricably linked to obesity, insulin resistance and cardiovascular disease. Here we summarize our current understanding of the role of the patatin-like phospholipase domain-containing 3 gene (PNPLA3) in hepatic steatosis. Recent findings: Multiple studies have revealed an association between the common I148M variant in PNPLA3 and increased hepatic fat. In the presence of obesity and chronic alcohol intake, the variant is associated with even more striking phenotypes such as hepatitis and cirrhosis, respectively. These findings suggest that genetic variants in PNPLA3 predispose towards hepatic steatosis and, in the context of other environmental stressors, its progression to irreversible liver failure. PNPLA3 is predominantly expressed in human liver and adipose tissue, possesses both lipolytic and lipogenic activity in vitro and localizes to the surface of lipid droplets in heptocytes. The 148M mutant protein has reduced lipolytic activity, with attendant increased cellular triglyceride accumulation. However, the precise physiological role of PNPLA3 remains mysterious. Summary: Recent studies have implicated PNPLA3 in the pathogenesis of hepatic steatosis. Attempts to describe its function in vivo may provide us with both an opportunity to understand and a strategy to overcome this leading cause of human morbidity.
MeSH term(s)	Animals ; Fatty Liver/enzymology ; Fatty Liver/etiology ; Fatty Liver/genetics ; Gene Expression Regulation, Enzymologic ; Humans ; Mutation ; Phospholipases A2, Calcium-Independent/genetics ; Phospholipases A2, Calcium-Independent/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	RNA, Messenger ; Phospholipases A2, Calcium-Independent (EC 3.1.1.4)
Language	English
Publishing date	2010-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1045394-5
ISSN	1473-6535 ; 0957-9672
ISSN (online)	1473-6535
ISSN	0957-9672
DOI	10.1097/mol.0b013e328338ca61
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Article: Rosiglitazone reduces liver fat and insulin requirements and improves hepatic insulin sensitivity and glycemic control in patients with type 2 diabetes requiring high insulin doses.

Juurinen, Leena / Kotronen, Anna / Granér, Marit / Yki-Järvinen, Hannele

The Journal of clinical endocrinology and metabolism

2008 Volume 93, Issue 1, Page(s) 118–124

Abstract: Background: Liver fat is an important determinant of insulin requirements during insulin therapy. Peroxisome proliferator-activated receptor (PPAR)-gamma agonists reduce liver fat. We therefore hypothesized that type 2 diabetic patients using ... ...

Abstract	Background: Liver fat is an important determinant of insulin requirements during insulin therapy. Peroxisome proliferator-activated receptor (PPAR)-gamma agonists reduce liver fat. We therefore hypothesized that type 2 diabetic patients using exceptionally high doses of insulin might respond well to addition of a PPARgamma agonist. Methods: We determined the effect of the PPARgamma agonist rosiglitazone on liver fat and directly measured hepatic insulin sensitivity in 14 patients with type 2 diabetes (aged 51 +/- 3 yr, body mass index 36.7 +/- 1.1 kg/m2), who were poorly controlled (glycosylated hemoglobin A 1c (HbA 1c) 8.9 +/- 0.4%) despite using high doses of insulin (218 +/- 22 IU/d) in combination with metformin. Liver fat content (1H-magnetic resonance spectroscopy), hepatic insulin sensitivity [6 h hyperinsulinemic euglycemic clamp (insulin 0.3 mU/kg.min) combined with [3-3H]glucose], body composition (magnetic resonance imaging), substrate oxidation rates (indirect calorimetry), clinical parameters, and liver enzymes were measured before and after rosiglitazone treatment (8 mg/d) for 8 months. Results: During rosiglitazone, HbA(1c) decreased from 8.9 +/- 0.4% to 7.8 +/- 0.3% (P = 0.007) and insulin requirements from 218 +/- 22 to 129 +/- 20 IU/d (P = 0.002). Liver fat content decreased by 46 +/- 9% from 20 +/- 3% to 11 +/- 3% (P = 0.0002). Hepatic insulin sensitivity, measured from the percent suppression of endogenous glucose production by insulin, increased from -40 +/- 7% to -89 +/- 12% (P = 0.001). The percent change in liver fat correlated with the percent decrease in HbA 1c (r = 0.53, P = 0.06), insulin dose (r = 0.66, P = 0.014), and suppression of endogenous glucose production (r = 0.76, P = 0.003). Conclusions: Our results suggest that rosiglitazone may be particularly effective in type 2 diabetic patients who are poorly controlled despite using high insulin doses. The mechanism is likely to involve reduced liver fat and enhanced hepatic insulin sensitivity.
MeSH term(s)	Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Blood Glucose/metabolism ; Body Composition ; Calorimetry, Indirect ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/enzymology ; Diabetes Mellitus, Type 2/metabolism ; Energy Metabolism ; Female ; Glucose Clamp Technique ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin/therapeutic use ; Liver/drug effects ; Liver/metabolism ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Oxidation-Reduction ; PPAR gamma/agonists ; Thiazolidinediones/therapeutic use
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Insulin ; PPAR gamma ; Thiazolidinediones ; rosiglitazone (05V02F2KDG)
Language	English
Publishing date	2008-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2007-1825
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Article: Fatty liver score and 15-year incidence of type 2 diabetes.

Kotronen, Anna / Laaksonen, Maarit A / Heliövaara, Markku / Reunanen, Antti / Tuomilehto, Jaakko / Yki-Järvinen, Hannele / Peltonen, Markku / Knekt, Paul

Hepatology international

2013 Volume 7, Issue 2, Page(s) 610–621

Abstract: Purpose: Both non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) are strongly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Recently, also the vitamin D level has been associated with these and may also ... ...

Abstract	Purpose: Both non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) are strongly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Recently, also the vitamin D level has been associated with these and may also be associated with fatty liver (FL). Liver function tests (LFTs) are insensitive markers of FL, but use of scores may help in identifying subjects with FL. We studied how LFTs and the FL score predict the development of T2DM in subjects with AFL versus NAFL and low versus high vitamin D levels. Methods: A cohort study based on 4,517 participants, aged 40-79, from the representative Mini-Finland Health Survey was carried out. During a follow-up of 15 years, 217 T2DM cases occurred. LFTs were determined from serum samples, and the FL score was formed using BMI, fasting glucose, HDL cholesterol, and GGT concentrations. Results: The risk of T2DM incidence in the highest versus lowest quartile was twofold for the LFTs and ninefold for the FL score. A total of 77 % (95 % confidence interval: 57-87 %) of the T2DM cases could have been prevented if all individuals' FL scores had been at the level of the first quartile. Heavy alcohol consumption and low serum vitamin D concentrations were associated with an increased risk of T2DM among individuals with high FL scores. Conclusions: The FL score is a useful tool for diagnosing FL in epidemiological studies. A high FL score predicts increased risk of T2DM, especially when combined with heavy alcohol consumption or low vitamin D levels.
Language	English
Publishing date	2013-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2270316-0
ISSN	1936-0541 ; 1936-0533
ISSN (online)	1936-0541
ISSN	1936-0533
DOI	10.1007/s12072-013-9430-7
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Article ; Online: Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum.

Kotronen, Anna / Seppänen-Laakso, Tuulikki / Westerbacka, Jukka / Kiviluoto, Tuula / Arola, Johanna / Ruskeepää, Anna-Liisa / Yki-Järvinen, Hannele / Oresic, Matej

Obesity (Silver Spring, Md.)

2010 Volume 18, Issue 5, Page(s) 937–944

Abstract: Ceramides may mediate saturated fat-induced insulin resistance, but there are no data comparing ceramide concentrations between human tissues. We therefore performed lipidomic analysis of human subcutaneous (SCfat) and intra-abdominal (IAfat) adipose ... ...

Abstract	Ceramides may mediate saturated fat-induced insulin resistance, but there are no data comparing ceramide concentrations between human tissues. We therefore performed lipidomic analysis of human subcutaneous (SCfat) and intra-abdominal (IAfat) adipose tissue, the liver, and serum in eight subjects. The liver contained (nmol/mg tissue) significantly more ceramides (1.5-3-fold), sphingomyelins (7-8-fold), phosphatidylethanolamines (10-11-fold), lysophosphatidylcholines (7-12-fold), less ether-linked phosphatidylcholines (2-2.5-fold) but similar amounts of diacylglycerols as compared to SCfat and IAfat. The amounts of ceramides and their synthetic precursors, such as palmitic (16:0) free fatty acids and sphingomyelins, differed considerably between the tissues. The liver contained proportionally more palmitic, stearic (18:0), and long polyunsaturated fatty acids than adipose tissues. Stearoyl-CoA desaturase 1 (SCD1) activity reflected by serum, estimated from the 16:1/16:0-ratio, was closely related to that in the liver (r = 0.86, P = 0.024) but not adipose tissues. This was also true for estimated elongase (18:1/16:1, r = 0.89, P = 0.01), and Delta5 (20:4/20:3, r = 0.89, P = 0.012) and Delta6 (18:3[n-6]/18:2, r = 1.0, P < 0.001) desaturase activities. We conclude that the human liver contains higher concentrations of ceramides and saturated free fatty acids than either SCfat or IAfat.
MeSH term(s)	Adult ; Analysis of Variance ; Female ; Humans ; Intra-Abdominal Fat/chemistry ; Lipids/analysis ; Lipids/blood ; Liver/chemistry ; Male ; Middle Aged ; Patient Selection ; Subcutaneous Fat/chemistry
Chemical Substances	Lipids
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1038/oby.2009.326
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Zs.A 4061: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes.

Kotronen, Anna / Juurinen, Leena / Tiikkainen, Mirja / Vehkavaara, Satu / Yki-Järvinen, Hannele

Gastroenterology

2008 Volume 135, Issue 1, Page(s) 122–130

Abstract: Background & aims: Liver fat is increased in type 2 diabetes. We determined whether it is associated with impaired insulin clearance and to what extent insulin resistance, impaired insulin clearance, or secretion contribute to fasting hyperinsulinemia. ... ...

Abstract	Background & aims: Liver fat is increased in type 2 diabetes. We determined whether it is associated with impaired insulin clearance and to what extent insulin resistance, impaired insulin clearance, or secretion contribute to fasting hyperinsulinemia. We also examined whether insulin suppression of serum free fatty acid (FFA) correlates with liver fat. Methods: We compared 68 type 2 diabetic patients and age-, gender-, and body mass index (BMI)-matched nondiabetic subjects. Liver fat was determined by (1)H-MRS, body composition by magnetic resonance imaging, and insulin clearance and action on hepatic glucose production (HGP), glucose uptake, and serum FFA by the euglycemic insulin clamp technique (insulin 0.3 mU/kg x min) combined with infusion of [3-(3)H]glucose. Results: Liver fat was 54% higher and insulin clearance 24% lower in type 2 diabetic patients than nondiabetic subjects. The percent suppression of both HGP and serum FFA by insulin were comparable, but serum insulin concentrations were significantly higher (34 mU/L [interquartile range, 30-39 mU/L] vs 25 mU/L [interquartile range, 22-30 mU/L]; P < .0001) in the type 2 diabetic than the nondiabetic subjects. When this difference was taken into account, both hepatic and adipose tissue insulin sensitivity were impaired in the type 2 diabetic subjects. Liver fat correlated with insulin clearance (r = -0.41; P = .001), and hepatic (r = 0.46; P = .0001) and adipose tissue (r = 0.55; P < .0001) insulin sensitivity. Hepatic but not peripheral insulin sensitivity was independently associated with liver fat content. Insulin clearance and secretion were independent determinants of fasting serum insulin. Conclusions: We conclude that increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance characterize type 2 diabetic patients.
MeSH term(s)	Adipose Tissue/metabolism ; Adult ; Body Mass Index ; Diabetes Mellitus, Type 2/metabolism ; Fatty Acids, Nonesterified/blood ; Fatty Liver/metabolism ; Fatty Liver/pathology ; Female ; Glucose Clamp Technique ; Humans ; Hyperinsulinism/metabolism ; Insulin/blood ; Insulin Resistance ; Liver/metabolism ; Liver/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Protons ; Regression Analysis
Chemical Substances	Fatty Acids, Nonesterified ; Insulin ; Protons
Language	English
Publishing date	2008-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2008.03.021
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Ui V Zs.44: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Insulin-like growth factor binding protein 1 as a novel specific marker of hepatic insulin sensitivity.

Kotronen, Anna / Lewitt, Moira / Hall, Kerstin / Brismar, Kerstin / Yki-Järvinen, Hannele

The Journal of clinical endocrinology and metabolism

2008 Volume 93, Issue 12, Page(s) 4867–4872

Abstract: Background and aims: The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat ... ...

Abstract	Background and aims: The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat content in humans. Methods: We measured fasting serum (fS) IGFBP-1 concentrations and liver fat content by proton magnetic resonance spectroscopy in 113 nondiabetic subjects. In addition, hepatic insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg.min) technique in combination with the infusion of [3-(3)H]glucose in 78 subjects. Results: fS-IGFBP-1 concentrations were inversely related to liver fat content (r = -0.38, P < 0.0001). Of circulating parameters, fS-IGFBP-1 was better correlated to hepatic insulin sensitivity (r = 0.48, P < 0.0001) than fS-insulin (r = -0.42, P = 0.0001), fS-C-peptide (r = -0.41, P = 0.0002), fS-triglyceride (r = -0.33, P = 0.003), or fS-high-density lipoprotein cholesterol (r = 0.30, P = 0.007). In multiple linear regression analyses, body mass index (P < 0.0001) and fS-IGFBP-1 (P = 0.008), but neither age nor gender, were independently associated with hepatic insulin sensitivity (P < 0.0001 for ANOVA). Neither fS-insulin nor fS-C-peptide were independent determinants of hepatic insulin sensitivity after adjusting for age, gender, and body mass index. Conclusions: fS-IGFBP-1 is inversely correlated with liver fat and is an obesity-independent and liver-specific circulating marker of hepatic insulin sensitivity.
MeSH term(s)	Adolescent ; Adult ; Aging/metabolism ; Biomarkers ; Blood Glucose/metabolism ; Body Composition ; Body Mass Index ; C-Peptide/blood ; Female ; Humans ; Hypoglycemic Agents/pharmacology ; Insulin/metabolism ; Insulin/pharmacology ; Insulin Resistance/physiology ; Insulin-Like Growth Factor Binding Protein 1/blood ; Lipid Metabolism ; Lipids/blood ; Liver/metabolism ; Liver/physiology ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Sex Characteristics ; Waist Circumference
Chemical Substances	Biomarkers ; Blood Glucose ; C-Peptide ; Hypoglycemic Agents ; Insulin ; Insulin-Like Growth Factor Binding Protein 1 ; Lipids
Language	English
Publishing date	2008-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2008-1245
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Article ; Online: Long-term effect of bariatric surgery on liver enzymes in the Swedish Obese Subjects (SOS) study.

Burza, Maria Antonella / Romeo, Stefano / Kotronen, Anna / Svensson, Per-Arne / Sjöholm, Kajsa / Torgerson, Jarl S / Lindroos, Anna-Karin / Sjöström, Lars / Carlsson, Lena M S / Peltonen, Markku

PloS one

2013 Volume 8, Issue 3, Page(s) e60495

Abstract: Background and aim: Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim ... ...

Abstract	Background and aim: Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals. Methods: The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups. Results: Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up. Conclusions: Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.
MeSH term(s)	Adult ; Bariatric Surgery ; Body Weight ; Female ; Follow-Up Studies ; Humans ; Liver/enzymology ; Male ; Middle Aged ; Obesity/blood ; Obesity/epidemiology ; Obesity/surgery ; Prospective Studies ; Sweden/epidemiology ; Time ; Transaminases/blood
Chemical Substances	Transaminases (EC 2.6.1.-)
Language	English
Publishing date	2013-03-26
Publishing country	United States
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0060495
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Article ; Online: Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver.

Kotronen, Anna / Seppänen-Laakso, Tuulikki / Westerbacka, Jukka / Kiviluoto, Tuula / Arola, Johanna / Ruskeepää, Anna-Liisa / Oresic, Matej / Yki-Järvinen, Hannele

Diabetes

2009 Volume 58, Issue 1, Page(s) 203–208

Abstract: Objective: To determine whether 1) hepatic ceramide and diacylglycerol concentrations, 2) SCD1 activity, and 3) hepatic lipogenic index are increased in the human nonalcoholic fatty liver.: Research design and methods: We studied 16 subjects with (n = ...

Abstract	Objective: To determine whether 1) hepatic ceramide and diacylglycerol concentrations, 2) SCD1 activity, and 3) hepatic lipogenic index are increased in the human nonalcoholic fatty liver. Research design and methods: We studied 16 subjects with (n = 8) and without (n = 8) histologically determined nonalcoholic fatty liver (NAFL(+) and NAFL(-)) matched for age, sex, and BMI. Hepatic concentrations of lipids and fatty acids were quantitated using ultra-performance liquid chromatography coupled to mass spectrometry and gas chromatography. Results: The absolute (nmol/mg) hepatic concentrations of diacylglycerols but not ceramides were increased in the NAFL(+) group compared with the NAFL(-) group. The livers of the NAFL(+) group contained proportionally less long-chain polyunsaturated fatty acids as compared with the NAFL(-) group. Liver fat percent was positively related to hepatic stearoyl-CoA desaturase 1 (SCD1) activity index (r = 0.70, P = 0.003) and the hepatic lipogenic index (r = 0.54, P = 0.030). Hepatic SCD1 activity index was positively related to the concentrations of diacylglycerols (r = 0.71, P = 0.002) but not ceramides (r = 0.07, NS). Conclusions: We conclude that diacylglycerols but not ceramides are increased in NAFL. The human fatty liver is also characterized by depletion of long polyunsaturated fatty acids in the liver and increases in hepatic SCD1 and lipogenic activities.
MeSH term(s)	Adolescent ; Adult ; Aged ; Ceramides/metabolism ; Chromatography, Liquid ; Diglycerides/metabolism ; Fatty Liver/enzymology ; Fatty Liver/metabolism ; Fatty Liver/pathology ; Female ; Humans ; Male ; Mass Spectrometry ; Middle Aged ; Stearoyl-CoA Desaturase/metabolism ; Young Adult
Chemical Substances	Ceramides ; Diglycerides ; Stearoyl-CoA Desaturase (EC 1.14.19.1)
Language	English
Publishing date	2009-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db08-1074
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