Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway

Joo Pin Foo, Konstantinos N. Aronis, John P. Chamberland, Jason Paruthi, Hyun-Seuk Moon, Christos S. Mantzoros

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

OBJECTIVE-Fibroblast growth factor (FGF)-21 is an endocrine factor with potentmetabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated.We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assesswhether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. RESEARCH DESIGN AND METHODS-Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 A.M. on day 4 until 8:00 A.M. on day 5. RESULTS-FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. CONCLUSIONS-A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close crosscorrelations with FFA in both fed state and energy deprivation, needs to be studied further.

Original languageEnglish
Pages (from-to)935-942
Number of pages8
JournalDiabetes Care
Volume36
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1
Externally publishedYes

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Leptin
Nonesterified Fatty Acids
Fasting
fibroblast growth factor 21
Lipolysis
Entropy
Starvation
Cross-Over Studies
Research Design
Placebos
Diet

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway. / Foo, Joo Pin; Aronis, Konstantinos N.; Chamberland, John P.; Paruthi, Jason; Moon, Hyun-Seuk; Mantzoros, Christos S.

In: Diabetes Care, Vol. 36, No. 4, 01.04.2013, p. 935-942.

Research output: Contribution to journalArticle

Foo, Joo Pin ; Aronis, Konstantinos N. ; Chamberland, John P. ; Paruthi, Jason ; Moon, Hyun-Seuk ; Mantzoros, Christos S. / Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway. In: Diabetes Care. 2013 ; Vol. 36, No. 4. pp. 935-942.
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abstract = "OBJECTIVE-Fibroblast growth factor (FGF)-21 is an endocrine factor with potentmetabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated.We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assesswhether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. RESEARCH DESIGN AND METHODS-Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 A.M. on day 4 until 8:00 A.M. on day 5. RESULTS-FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. CONCLUSIONS-A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close crosscorrelations with FFA in both fed state and energy deprivation, needs to be studied further.",
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AU - Foo, Joo Pin

AU - Aronis, Konstantinos N.

AU - Chamberland, John P.

AU - Paruthi, Jason

AU - Moon, Hyun-Seuk

AU - Mantzoros, Christos S.

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N2 - OBJECTIVE-Fibroblast growth factor (FGF)-21 is an endocrine factor with potentmetabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated.We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assesswhether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. RESEARCH DESIGN AND METHODS-Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 A.M. on day 4 until 8:00 A.M. on day 5. RESULTS-FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. CONCLUSIONS-A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close crosscorrelations with FFA in both fed state and energy deprivation, needs to be studied further.

AB - OBJECTIVE-Fibroblast growth factor (FGF)-21 is an endocrine factor with potentmetabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated.We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assesswhether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. RESEARCH DESIGN AND METHODS-Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 A.M. on day 4 until 8:00 A.M. on day 5. RESULTS-FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. CONCLUSIONS-A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close crosscorrelations with FFA in both fed state and energy deprivation, needs to be studied further.

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