Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates

Subhash Kamath, Alberto O. Chavez, Amalia Gastaldelli, Francesca Casiraghi, Glenn A. Halff, Gregory A. Abrahamian, Alberto M. Davalli, Raul A. Bastarrachea, Anthony G. Comuzzie, Rodolfo Guardado-Mendoza, Lilia M. Jimenez-Ceja, Vicki Mattern, Ana Maria Paez, Andrea Ricotti, Mary E. Tejero, Paul B. Higgins, Iram Pablo Rodriguez-Sanchez, Devjit Tripathy, Ralph A. DeFronzo, Edward J. Dick & 2 others Gary W. Cline, Franco Folli

Research output: Contribution to journalArticle

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Abstract

Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant. Aims: To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity. Methods: Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance. Results: Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons. Conclusion: Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.

Original languageEnglish
Article numbere27617
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - 2011

Fingerprint

fatty acid metabolism
long chain fatty acids
Metabolism
insulin resistance
Primates
Insulin Resistance
Liver
Triglycerides
Fatty Acids
triacylglycerols
Insulin
Defects
liver
fatty liver
Papio
Acyl Coenzyme A
insulin
adiposity
Adiposity
Biomarkers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kamath, S., Chavez, A. O., Gastaldelli, A., Casiraghi, F., Halff, G. A., Abrahamian, G. A., ... Folli, F. (2011). Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates. PLoS One, 6(11), [e27617]. https://doi.org/10.1371/journal.pone.0027617

Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates. / Kamath, Subhash; Chavez, Alberto O.; Gastaldelli, Amalia; Casiraghi, Francesca; Halff, Glenn A.; Abrahamian, Gregory A.; Davalli, Alberto M.; Bastarrachea, Raul A.; Comuzzie, Anthony G.; Guardado-Mendoza, Rodolfo; Jimenez-Ceja, Lilia M.; Mattern, Vicki; Paez, Ana Maria; Ricotti, Andrea; Tejero, Mary E.; Higgins, Paul B.; Rodriguez-Sanchez, Iram Pablo; Tripathy, Devjit; DeFronzo, Ralph A.; Dick, Edward J.; Cline, Gary W.; Folli, Franco.

In: PLoS One, Vol. 6, No. 11, e27617, 2011.

Research output: Contribution to journalArticle

Kamath, S, Chavez, AO, Gastaldelli, A, Casiraghi, F, Halff, GA, Abrahamian, GA, Davalli, AM, Bastarrachea, RA, Comuzzie, AG, Guardado-Mendoza, R, Jimenez-Ceja, LM, Mattern, V, Paez, AM, Ricotti, A, Tejero, ME, Higgins, PB, Rodriguez-Sanchez, IP, Tripathy, D, DeFronzo, RA, Dick, EJ, Cline, GW & Folli, F 2011, 'Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates', PLoS One, vol. 6, no. 11, e27617. https://doi.org/10.1371/journal.pone.0027617
Kamath, Subhash ; Chavez, Alberto O. ; Gastaldelli, Amalia ; Casiraghi, Francesca ; Halff, Glenn A. ; Abrahamian, Gregory A. ; Davalli, Alberto M. ; Bastarrachea, Raul A. ; Comuzzie, Anthony G. ; Guardado-Mendoza, Rodolfo ; Jimenez-Ceja, Lilia M. ; Mattern, Vicki ; Paez, Ana Maria ; Ricotti, Andrea ; Tejero, Mary E. ; Higgins, Paul B. ; Rodriguez-Sanchez, Iram Pablo ; Tripathy, Devjit ; DeFronzo, Ralph A. ; Dick, Edward J. ; Cline, Gary W. ; Folli, Franco. / Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates. In: PLoS One. 2011 ; Vol. 6, No. 11.
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abstract = "Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant. Aims: To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity. Methods: Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance. Results: Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons. Conclusion: Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.",
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T1 - Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates

AU - Kamath, Subhash

AU - Chavez, Alberto O.

AU - Gastaldelli, Amalia

AU - Casiraghi, Francesca

AU - Halff, Glenn A.

AU - Abrahamian, Gregory A.

AU - Davalli, Alberto M.

AU - Bastarrachea, Raul A.

AU - Comuzzie, Anthony G.

AU - Guardado-Mendoza, Rodolfo

AU - Jimenez-Ceja, Lilia M.

AU - Mattern, Vicki

AU - Paez, Ana Maria

AU - Ricotti, Andrea

AU - Tejero, Mary E.

AU - Higgins, Paul B.

AU - Rodriguez-Sanchez, Iram Pablo

AU - Tripathy, Devjit

AU - DeFronzo, Ralph A.

AU - Dick, Edward J.

AU - Cline, Gary W.

AU - Folli, Franco

PY - 2011

Y1 - 2011

N2 - Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant. Aims: To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity. Methods: Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance. Results: Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons. Conclusion: Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.

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