Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: A role for ovarian hormones

Melissa N. Martinez, Christopher H. Emfinger, Matthew Overton, Salisha Hill, Tara S. Ramaswamy, David A. Cappel, Ke Wu, Sergio Fazio, W. Hayes McDonald, David L. Hachey, David L. Tabb, John M. Stafford

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Mechanisms underlying changes in HDL composition caused by obesity are poorly defined, partly because mice lack expression of cholesteryl ester transfer protein (CETP), which shuttles triglyceride and cholesteryl ester between lipoproteins. Because menopause is associated with weight gain, altered glucose metabolism, and changes in HDL, we tested the effect of feeding a high-fat diet (HFD) and ovariectomy (OVX) on glucose metabolism and HDL composition in CETP transgenic mice. After OVX, female CETP-expressing mice had accelerated weight gain with HFD-feeding and impaired glucose tolerance by hyperglycemic clamp techniques, compared with OVX mice fed a low-fat diet (LFD). Sham-operated mice (SHAM) did not show HFD-induced weight gain and had less glucose intolerance than OVX mice. Using shotgun HDL proteomics, HFD-feeding in OVX mice had a large effect on HDL composition, including increased levels of apoA2, apoA4, apoC2, and apoC3, proteins involved in TG metabolism. These changes were associated with decreased hepatic expression of SR-B1, ABCA1, and LDL receptor, proteins involved in modulating the lipid content of HDL. In SHAM mice, there were minimal changes in HDL composition with HFD feeding. These studies suggest that the absence of ovarian hormones negatively influences the response to high-fat feeding in terms of glucose tolerance and HDL composition. CETP-expressing mice may represent a useful model to define how metabolic changes affect HDL composition and function.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalJournal of Lipid Research
Volume53
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

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Cholesterol Ester Transfer Proteins
Metabolism
Transgenic Mice
Nutrition
Obesity
Fats
Hormones
High Fat Diet
Glucose
Chemical analysis
Weight Gain
Glucose Intolerance
Apolipoprotein C-II
Cholesterol Esters
LDL Receptors
Clamping devices
Fat-Restricted Diet
Firearms
Ovariectomy
Lipoproteins

Keywords

  • Cholesteryl ester transfer protein
  • High density lipoprotein
  • Hyperglycemic clamp
  • Menopause
  • Proteomics
  • Triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Martinez, M. N., Emfinger, C. H., Overton, M., Hill, S., Ramaswamy, T. S., Cappel, D. A., ... Stafford, J. M. (2012). Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: A role for ovarian hormones. Journal of Lipid Research, 53(3), 379-389. https://doi.org/10.1194/jlr.M019752

Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice : A role for ovarian hormones. / Martinez, Melissa N.; Emfinger, Christopher H.; Overton, Matthew; Hill, Salisha; Ramaswamy, Tara S.; Cappel, David A.; Wu, Ke; Fazio, Sergio; McDonald, W. Hayes; Hachey, David L.; Tabb, David L.; Stafford, John M.

In: Journal of Lipid Research, Vol. 53, No. 3, 03.2012, p. 379-389.

Research output: Contribution to journalArticle

Martinez, MN, Emfinger, CH, Overton, M, Hill, S, Ramaswamy, TS, Cappel, DA, Wu, K, Fazio, S, McDonald, WH, Hachey, DL, Tabb, DL & Stafford, JM 2012, 'Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: A role for ovarian hormones', Journal of Lipid Research, vol. 53, no. 3, pp. 379-389. https://doi.org/10.1194/jlr.M019752
Martinez, Melissa N. ; Emfinger, Christopher H. ; Overton, Matthew ; Hill, Salisha ; Ramaswamy, Tara S. ; Cappel, David A. ; Wu, Ke ; Fazio, Sergio ; McDonald, W. Hayes ; Hachey, David L. ; Tabb, David L. ; Stafford, John M. / Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice : A role for ovarian hormones. In: Journal of Lipid Research. 2012 ; Vol. 53, No. 3. pp. 379-389.
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abstract = "Mechanisms underlying changes in HDL composition caused by obesity are poorly defined, partly because mice lack expression of cholesteryl ester transfer protein (CETP), which shuttles triglyceride and cholesteryl ester between lipoproteins. Because menopause is associated with weight gain, altered glucose metabolism, and changes in HDL, we tested the effect of feeding a high-fat diet (HFD) and ovariectomy (OVX) on glucose metabolism and HDL composition in CETP transgenic mice. After OVX, female CETP-expressing mice had accelerated weight gain with HFD-feeding and impaired glucose tolerance by hyperglycemic clamp techniques, compared with OVX mice fed a low-fat diet (LFD). Sham-operated mice (SHAM) did not show HFD-induced weight gain and had less glucose intolerance than OVX mice. Using shotgun HDL proteomics, HFD-feeding in OVX mice had a large effect on HDL composition, including increased levels of apoA2, apoA4, apoC2, and apoC3, proteins involved in TG metabolism. These changes were associated with decreased hepatic expression of SR-B1, ABCA1, and LDL receptor, proteins involved in modulating the lipid content of HDL. In SHAM mice, there were minimal changes in HDL composition with HFD feeding. These studies suggest that the absence of ovarian hormones negatively influences the response to high-fat feeding in terms of glucose tolerance and HDL composition. CETP-expressing mice may represent a useful model to define how metabolic changes affect HDL composition and function.",
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AU - Ramaswamy, Tara S.

AU - Cappel, David A.

AU - Wu, Ke

AU - Fazio, Sergio

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