Cargando…
Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD)
Individuals with metabolic dysfunction–associated fatty liver disease (MAFLD) have elevated plasma lipids as well as glucagon, although glucagon suppresses hepatic VLDL-triglyceride (TG) secretion. We hypothesize that the sensitivity to glucagon in hepatic lipid metabolism is impaired in MAFLD. We r...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630084/ https://www.ncbi.nlm.nih.gov/pubmed/36001750 http://dx.doi.org/10.2337/db22-0313 |
_version_ | 1784823525461196800 |
---|---|
author | Heebøll, Sara Risikesan, Jeyanthini Ringgaard, Steffen Kumarathas, Indumathi Sandahl, Thomas D. Grønbæk, Henning Søndergaard, Esben Nielsen, Søren |
author_facet | Heebøll, Sara Risikesan, Jeyanthini Ringgaard, Steffen Kumarathas, Indumathi Sandahl, Thomas D. Grønbæk, Henning Søndergaard, Esben Nielsen, Søren |
author_sort | Heebøll, Sara |
collection | PubMed |
description | Individuals with metabolic dysfunction–associated fatty liver disease (MAFLD) have elevated plasma lipids as well as glucagon, although glucagon suppresses hepatic VLDL-triglyceride (TG) secretion. We hypothesize that the sensitivity to glucagon in hepatic lipid metabolism is impaired in MAFLD. We recruited 11 subjects with severe MAFLD (MAFLD+), 10 with mild MAFLD (MAFLD−), and 7 overweight control (CON) subjects. We performed a pancreatic clamp with a somatostatin analog (octreotide) to suppress endogenous hormone production, combined with infusion of low-dose glucagon (0.65 ng/kg/min, t = 0–270 min, LowGlucagon), followed by high-dose glucagon (1.5 ng/kg/min, t = 270–450 min, HighGlucagon). VLDL-TG and glucose tracers were used to evaluate VLDL-TG kinetics and endogenous glucose production (EGP). HighGlucagon suppressed VLDL-TG secretion compared with LowGlucagon. This suppression was markedly attenuated in MAFLD subjects compared with CON subjects (MAFLD+: 13% ± [SEM] 5%; MAFLD−: 10% ± 3%; CON: 36% ± 7%, P < 0.01), with no difference between MAFLD groups. VLDL-TG concentration and VLDL-TG oxidation rate increased between LowGlucagon and HighGlucagon in MAFLD+ subjects compared with CON subjects. EGP transiently increased during HighGlucagon without any difference between the three groups. Individuals with MAFLD have a reduced sensitivity to glucagon in the hepatic TG metabolism, which could contribute to the dyslipidemia seen in MAFLD patients. ClinicalTrials.gov: NCT04042142. |
format | Online Article Text |
id | pubmed-9630084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-96300842023-01-21 Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) Heebøll, Sara Risikesan, Jeyanthini Ringgaard, Steffen Kumarathas, Indumathi Sandahl, Thomas D. Grønbæk, Henning Søndergaard, Esben Nielsen, Søren Diabetes Pathophysiology Individuals with metabolic dysfunction–associated fatty liver disease (MAFLD) have elevated plasma lipids as well as glucagon, although glucagon suppresses hepatic VLDL-triglyceride (TG) secretion. We hypothesize that the sensitivity to glucagon in hepatic lipid metabolism is impaired in MAFLD. We recruited 11 subjects with severe MAFLD (MAFLD+), 10 with mild MAFLD (MAFLD−), and 7 overweight control (CON) subjects. We performed a pancreatic clamp with a somatostatin analog (octreotide) to suppress endogenous hormone production, combined with infusion of low-dose glucagon (0.65 ng/kg/min, t = 0–270 min, LowGlucagon), followed by high-dose glucagon (1.5 ng/kg/min, t = 270–450 min, HighGlucagon). VLDL-TG and glucose tracers were used to evaluate VLDL-TG kinetics and endogenous glucose production (EGP). HighGlucagon suppressed VLDL-TG secretion compared with LowGlucagon. This suppression was markedly attenuated in MAFLD subjects compared with CON subjects (MAFLD+: 13% ± [SEM] 5%; MAFLD−: 10% ± 3%; CON: 36% ± 7%, P < 0.01), with no difference between MAFLD groups. VLDL-TG concentration and VLDL-TG oxidation rate increased between LowGlucagon and HighGlucagon in MAFLD+ subjects compared with CON subjects. EGP transiently increased during HighGlucagon without any difference between the three groups. Individuals with MAFLD have a reduced sensitivity to glucagon in the hepatic TG metabolism, which could contribute to the dyslipidemia seen in MAFLD patients. ClinicalTrials.gov: NCT04042142. American Diabetes Association 2022-11 2022-08-24 /pmc/articles/PMC9630084/ /pubmed/36001750 http://dx.doi.org/10.2337/db22-0313 Text en © 2022 by the American Diabetes Association https://www.diabetesjournals.org/journals/pages/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license. |
spellingShingle | Pathophysiology Heebøll, Sara Risikesan, Jeyanthini Ringgaard, Steffen Kumarathas, Indumathi Sandahl, Thomas D. Grønbæk, Henning Søndergaard, Esben Nielsen, Søren Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title | Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title_full | Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title_fullStr | Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title_full_unstemmed | Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title_short | Impaired Glucagon-Mediated Suppression of VLDL-Triglyceride Secretion in Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) |
title_sort | impaired glucagon-mediated suppression of vldl-triglyceride secretion in individuals with metabolic dysfunction–associated fatty liver disease (mafld) |
topic | Pathophysiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630084/ https://www.ncbi.nlm.nih.gov/pubmed/36001750 http://dx.doi.org/10.2337/db22-0313 |
work_keys_str_mv | AT heebøllsara impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT risikesanjeyanthini impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT ringgaardsteffen impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT kumarathasindumathi impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT sandahlthomasd impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT grønbækhenning impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT søndergaardesben impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld AT nielsensøren impairedglucagonmediatedsuppressionofvldltriglyceridesecretioninindividualswithmetabolicdysfunctionassociatedfattyliverdiseasemafld |