TY - JOUR
T1 - Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans
AU - Apostolopoulou, Maria
AU - Gordillo, Ruth
AU - Gancheva, Sofiya
AU - Strassburger, Klaus
AU - Herder, Christian
AU - Esposito, Irene
AU - Schlensak, Matthias
AU - Scherer, Philipp E.
AU - Roden, Michael
N1 - Publisher Copyright:
© 2020 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2020/11/20
Y1 - 2020/11/20
N2 - Introduction Sphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans. Research design and methods Thus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery. Results Surprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation. Conclusion These results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.
AB - Introduction Sphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans. Research design and methods Thus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery. Results Surprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation. Conclusion These results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.
KW - inflammation
KW - insulin resistance
KW - non-alcoholic fatty liver disease
KW - obesity
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U2 - 10.1136/bmjdrc-2020-001860
DO - 10.1136/bmjdrc-2020-001860
M3 - Article
C2 - 33219119
AN - SCOPUS:85096814658
SN - 2052-4897
VL - 8
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
IS - 2
M1 - e001860
ER -