Lipin deficiency impairs diurnal metabolic fuel switching

Jun Xu, W. N Paul Lee, Jack Phan, Mohammed F. Saad, Karen Reue, Irwin J. Kurland

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Fatty liver is a common feature of both obesity and lipodystrophy, reflecting compromised adipose tissue function. The lipin-deficient fatty liver dystrophy (fld) mouse is an exception, as there is lipodystrophy without a fatty liver. Using a combination of indirect calorimetry and stable-isotope flux phenotyping, we determined that fld mice exhibit abnormal fuel utilization throughout the diurnal cycle, with increased glucose oxidation near the end of the fasting period and increased fatty acid oxidation during the feeding period. The mechanisms underlying these alterations include a twofold increase compared with wild-type mice in tissue glycogen storage during the fed state, a 40% reduction in hepatic glucose production in the fasted state, and a 27-fold increase in de novo fatty acid synthesis in liver during the fed state. Thus, the inability to store energy in adipose tissue in the fld mouse leads to a compensatory increase in glycogen storage for use during the fasting period and reliance upon hepatic fatty acid synthesis to provide fuel for peripheral tissues during the fed state. The increase in hepatic fatty acid synthesis and peripheral utilization provides a potential mechanism to ameliorate fatty liver in the fld that would otherwise occur as a consequence of adipose tissue dysfunction.

Original languageEnglish (US)
Pages (from-to)3429-3438
Number of pages10
JournalDiabetes
Volume55
Issue number12
DOIs
StatePublished - Dec 2006
Externally publishedYes

Fingerprint

Fatty Liver
Fatty Acids
Lipodystrophy
Adipose Tissue
Liver
Glycogen
Fasting
Glucose
Indirect Calorimetry
lipine
Isotopes
Obesity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Xu, J., Lee, W. N. P., Phan, J., Saad, M. F., Reue, K., & Kurland, I. J. (2006). Lipin deficiency impairs diurnal metabolic fuel switching. Diabetes, 55(12), 3429-3438. https://doi.org/10.2337/db06-0260

Lipin deficiency impairs diurnal metabolic fuel switching. / Xu, Jun; Lee, W. N Paul; Phan, Jack; Saad, Mohammed F.; Reue, Karen; Kurland, Irwin J.

In: Diabetes, Vol. 55, No. 12, 12.2006, p. 3429-3438.

Research output: Contribution to journalArticle

Xu, J, Lee, WNP, Phan, J, Saad, MF, Reue, K & Kurland, IJ 2006, 'Lipin deficiency impairs diurnal metabolic fuel switching', Diabetes, vol. 55, no. 12, pp. 3429-3438. https://doi.org/10.2337/db06-0260
Xu, Jun ; Lee, W. N Paul ; Phan, Jack ; Saad, Mohammed F. ; Reue, Karen ; Kurland, Irwin J. / Lipin deficiency impairs diurnal metabolic fuel switching. In: Diabetes. 2006 ; Vol. 55, No. 12. pp. 3429-3438.
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