Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome.
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Aims/hypothesis The aim of this study was to investigate whether intrahepatic and intramyocellular fat are related to insulin resistance in these respective tissues or to the metabolic syndrome.Methods Hepatic (insulin 1.8 pmol kg(-1) min(-1) combined with [3-3H]glucose) and muscle (insulin 6.0 pmol kg(-1) min(-1)) insulin sensitivity were measured on separate occasions in 45 non-diabetic men (age 42 +/- 1 years, BMI 26.2 +/- 0.6 kg/m2) using the euglycaemic-hyperinsulinaemic clamp. Liver fat and intramyocellular lipid (IMCL) were measured by proton magnetic resonance spectroscopy and body composition by magnetic resonance imaging. We also determined fasting serum insulin and adiponectin concentrations, components of the metabolic syndrome and maximal oxygen consumption.Results In participants with high [median 12.0% (interquartile range 5.7-18.5%)] vs low [2.0% (1.0-2.0%)] liver fat, fasting serum triacylglycerols (1.6 +/- 0.2 vs 1.0 +/- 0.1 mmol/l, p = 0.002) and fasting serum insulin (55 +/- 4 vs 32 +/- 2 pmol/l, p < 0.0001) were increased and serum HDL-cholesterol (1.26 +/- 0.1 vs 1.48 +/- 0.1 mmol/l, p = 0.02) and fasting serum adiponectin (9.5 +/- 1.2 vs 12.2 +/- 1.2 microg/ml, p = 0.05) decreased. In participants with high [19.5% (16.0-26.0%)] vs low [5.0% (2.3-7.5%)] IMCL, these parameters were comparable. Liver fat was higher in participants with [10.5% (3.0-18.0%)] than in those without [2.0% (1.5-6.0%), p = 0.010] the metabolic syndrome, even independently of obesity, while IMCL was comparable. Insulin suppression of glucose rate of appearance and serum NEFA was significantly impaired in the high liver fat group.Conclusions/interpretation Fat accumulation in the liver rather than in skeletal muscle is associated with features of the metabolic syndrome, i.e. increased fasting serum triacylglycerols and decreased fasting serum HDL-cholesterol, as well as with hyperinsulinaemia and low adiponectin.
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Lipid accumulation in hepatocytes is linked to insulin resistance and the development of type 2 diabetes.
“Lipid accumulation in hepatocytes has been linked to insulin resistance and the development of T2DM158.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [158]
Recent human data have highlighted the importance of disordered hepatic metabolism, including inappropriately increased hepatic glucose production, hyperlipidemia, and lipid accumulation, in both obesity and type 2 DM.
“Recent human data have highlighted the importance of disordered hepatic metabolism, including inappropriately increased hepatic glucose production, hyperlipidemia, and lipid accumulation, in both obesity and type 2 DM (207).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [207]
Accumulation of lipid within hepatocytes is a key marker of insulin resistance in humans and a major contributor to nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), and cirrhosis.
“Because accumulation of lipid within hepatocytes is a key marker of insulin resistance in humans (207) and a major contributor to nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), and cirrhosis, we will first consider relationships between hepatic lipid metabolism and insulin resistance, and in Section III.C.3 will review evidence linking DM and hepatic steatosis to”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [207]
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- Authors
- Kotronen, A., Seppälä-Lindroos, A., Bergholm, R., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Kotronen, A.
- Venue
- Diabetologia
- Published
- 2007-11-16
- Volume
- 51
- Issue
- 1
- Pages
- 130-138
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2053697048
- Cited by
- 126
- References
- 47
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 5 · 2014: 7 · 2013: 12 · 2012: 9
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission (LSHM‐CT‐2005‐018734)
- Academy of Finland
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- insulin resistance, liver fat, intramyocellular lipid, tissue specificity, metabolic syndrome, insulin sensitivity, hepatic insulin sensitivity, skeletal muscle insulin sensitivity, adiponectin, HDL cholesterol, triglycerides, free fatty acids, hyperinsulinemic-euglycemic clamp, 1H NMR, body composition, VO2max
- MeSH terms
- Adult, Body Composition, Cholesterol, Glucose, Humans, Insulin, Insulin Resistance, Liver, Male, Middle Aged, Muscles, Magnetic Resonance Spectroscopy, Obesity, Body Mass Index, Metabolic Syndrome
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