Differential effects of Calca-derived peptides in male mice with diet-induced obesity
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Differential effects of Calca-derived peptides in male mice with diet-induced obesity. / Bartelt, Alexander; Jeschke, Anke; Müller, Brigitte; Gaziano, Isabella; Morales, Michelle; Yorgan, Timur; Heckt, Timo; Heine, Markus; Gagel, Robert F; Emeson, Ronald B; Amling, Michael; Niemeier, Andreas; Heeren, Jörg; Schinke, Thorsten; Keller, Johannes.
In: PLOS ONE, Vol. 12, No. 6, 2017, p. e0180547.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Differential effects of Calca-derived peptides in male mice with diet-induced obesity
AU - Bartelt, Alexander
AU - Jeschke, Anke
AU - Müller, Brigitte
AU - Gaziano, Isabella
AU - Morales, Michelle
AU - Yorgan, Timur
AU - Heckt, Timo
AU - Heine, Markus
AU - Gagel, Robert F
AU - Emeson, Ronald B
AU - Amling, Michael
AU - Niemeier, Andreas
AU - Heeren, Jörg
AU - Schinke, Thorsten
AU - Keller, Johannes
PY - 2017
Y1 - 2017
N2 - Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr-/- (encoding the calcitonin receptor, CTR), Calca-/-, and αCGRP-/- mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. HFD-induced pathologies were assessed by glucose tolerance, plasma cytokine and lipid markers, expression studies and histology. We found that DIO in mice lacking the CTR resulted in impaired glucose tolerance, features of enhanced nonalcoholic steatohepatitis (NASH) and adipose tissue inflammation compared to wildtype littermates. Furthermore, CTR-deficient mice were characterized by dyslipidemia and elevated HDL levels. In contrast, mice lacking Calca were protected from DIO, NASH and adipose tissue inflammation, and displayed improved glucose tolerance. Mice exclusively lacking αCGRP displayed a significantly less improved DIO phenotype compared to Calca-deficient mice. In summary, we demonstrate that the CT/CTR axis is involved in regulating plasma cholesterol levels while Calca, presumably through PCT, seems to have a detrimental effect in the context of metabolic disease. Our study provides the first comparative analyses of the roles of Calca-derived peptides and the CTR in metabolic disease.
AB - Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr-/- (encoding the calcitonin receptor, CTR), Calca-/-, and αCGRP-/- mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. HFD-induced pathologies were assessed by glucose tolerance, plasma cytokine and lipid markers, expression studies and histology. We found that DIO in mice lacking the CTR resulted in impaired glucose tolerance, features of enhanced nonalcoholic steatohepatitis (NASH) and adipose tissue inflammation compared to wildtype littermates. Furthermore, CTR-deficient mice were characterized by dyslipidemia and elevated HDL levels. In contrast, mice lacking Calca were protected from DIO, NASH and adipose tissue inflammation, and displayed improved glucose tolerance. Mice exclusively lacking αCGRP displayed a significantly less improved DIO phenotype compared to Calca-deficient mice. In summary, we demonstrate that the CT/CTR axis is involved in regulating plasma cholesterol levels while Calca, presumably through PCT, seems to have a detrimental effect in the context of metabolic disease. Our study provides the first comparative analyses of the roles of Calca-derived peptides and the CTR in metabolic disease.
KW - Animals
KW - Calcitonin Gene-Related Peptide
KW - Diet, High-Fat
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Obesity
KW - Peptides
KW - Journal Article
U2 - 10.1371/journal.pone.0180547
DO - 10.1371/journal.pone.0180547
M3 - SCORING: Journal article
C2 - 28666011
VL - 12
SP - e0180547
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
ER -
