Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

Panu K Luukkonen; Sanja Sädevirta; You Zhou; Brandon Kayser; Ashfaq Ali; Linda Ahonen; Susanna Lallukka; Véronique Pelloux; Melania Gaggini; Ching Jian; Antti Hakkarainen; Nina Lundbom; Helena Gylling; Anne Salonen; Matej Orešič; Tuulia Hyötyläinen; Marju Orho-Melander; Aila Rissanen; Amalia Gastaldelli; Karine Clément; Leanne Hodson; Hannele Yki-Järvinen

doi:10.2337/dc18-0071

Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

Panu K Luukkonen, Sanja Sädevirta, You Zhou, Brandon Kayser, Ashfaq Ali, Linda Ahonen, Susanna Lallukka, Véronique Pelloux, Melania Gaggini, Ching Jian, Antti Hakkarainen, Nina Lundbom, Helena Gylling, Anne Salonen, Matej Orešič, Tuulia Hyötyläinen, Marju Orho-Melander, Aila Rissanen, Amalia Gastaldelli, Karine ClémentLeanne Hodson, Hannele Yki-Järvinen

Steno Diabetes Center Copenhagen

373 Citations (Scopus)

Abstract

OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.

RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.

RESULTS: Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.

CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.

Original language	English
Journal	Diabetes Care
Volume	41
Issue number	7
ISSN	1935-5548
DOIs	https://doi.org/10.2337/dc18-0071
Publication status	Published - Jul 2018

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Luukkonen, P. K., Sädevirta, S., Zhou, Y., Kayser, B., Ali, A., Ahonen, L., Lallukka, S., Pelloux, V., Gaggini, M., Jian, C., Hakkarainen, A., Lundbom, N., Gylling, H., Salonen, A., Orešič, M., Hyötyläinen, T., Orho-Melander, M., Rissanen, A., Gastaldelli, A., ... Yki-Järvinen, H. (2018). Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars. Diabetes Care, 41(7). https://doi.org/10.2337/dc18-0071

Luukkonen, PK, Sädevirta, S, Zhou, Y, Kayser, B, Ali, A, Ahonen, L, Lallukka, S, Pelloux, V, Gaggini, M, Jian, C, Hakkarainen, A, Lundbom, N, Gylling, H, Salonen, A, Orešič, M, Hyötyläinen, T, Orho-Melander, M, Rissanen, A, Gastaldelli, A, Clément, K, Hodson, L & Yki-Järvinen, H 2018, 'Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars', Diabetes Care, vol. 41, no. 7. https://doi.org/10.2337/dc18-0071

@article{d7bf45e75d4a4cf8acd14a4b59da100a,

title = "Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars",

abstract = "OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9\%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.RESULTS: Overfeeding SAT increased IHTG more (+55\%) than UNSAT (+15\%, P < 0.05). CARB increased IHTG (+33\%) by stimulating DNL (+98\%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.",

author = "Luukkonen, \{Panu K\} and Sanja S{\"a}devirta and You Zhou and Brandon Kayser and Ashfaq Ali and Linda Ahonen and Susanna Lallukka and V{\'e}ronique Pelloux and Melania Gaggini and Ching Jian and Antti Hakkarainen and Nina Lundbom and Helena Gylling and Anne Salonen and Matej Ore{\v s}i{\v c} and Tuulia Hy{\"o}tyl{\"a}inen and Marju Orho-Melander and Aila Rissanen and Amalia Gastaldelli and Karine Cl{\'e}ment and Leanne Hodson and Hannele Yki-J{\"a}rvinen",

note = "{\textcopyright} 2018 by the American Diabetes Association.",

year = "2018",

month = jul,

doi = "10.2337/dc18-0071",

language = "English",

volume = "41",

journal = "Diabetes Care",

issn = "1935-5548",

publisher = "American Diabetes Association",

number = "7",

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TY - JOUR

T1 - Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

AU - Luukkonen, Panu K

AU - Sädevirta, Sanja

AU - Zhou, You

AU - Kayser, Brandon

AU - Ali, Ashfaq

AU - Ahonen, Linda

AU - Lallukka, Susanna

AU - Pelloux, Véronique

AU - Gaggini, Melania

AU - Jian, Ching

AU - Hakkarainen, Antti

AU - Lundbom, Nina

AU - Gylling, Helena

AU - Salonen, Anne

AU - Orešič, Matej

AU - Hyötyläinen, Tuulia

AU - Orho-Melander, Marju

AU - Rissanen, Aila

AU - Gastaldelli, Amalia

AU - Clément, Karine

AU - Hodson, Leanne

AU - Yki-Järvinen, Hannele

PY - 2018/7

Y1 - 2018/7

N2 - OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.RESULTS: Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.

AB - OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.RESULTS: Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.

UR - https://www.scopus.com/pages/publications/85052752226

U2 - 10.2337/dc18-0071

DO - 10.2337/dc18-0071

M3 - Journal article

C2 - 29844096

SN - 1935-5548

VL - 41

JO - Diabetes Care

JF - Diabetes Care

IS - 7

ER -

Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars

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