Fibroblast growth factor 21, fibroblast growth factor receptor 1, and β-Klotho expression in bovine growth hormone transgenic and growth hormone receptor knockout mice

Brooks, Nicole E.; Hjortebjerg, Rikke; Henry, Brooke E.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

doi:10.1016/j.ghir.2016.08.003

Cited by 16 publications

(9 citation statements)

References 56 publications

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“…iWAT, which would decrease the ability of the tissue to respond to FGF21. It should be noted that while the current study observed decreased circulating FGF21 in GHR-/-mice, Brooks et al [61] report no changes to circulating FGF21 in GHR-/-mice. While we cannot explain the this difference, it could be due to factors such as age of mice as we evaluated 16 week old GHR-/mice while mice from Brooks et al were nearly twice that age.…”

Section: Accepted Manuscriptcontrasting

confidence: 83%

Growth hormone activated STAT5 is required for induction of beige fat in vivo

Nelson

List

Ieremia

et al. 2018

Growth Hormone & IGF Research

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Section: Accepted Manuscriptcontrasting

confidence: 83%

Growth hormone activated STAT5 is required for induction of beige fat in vivo

Nelson

List

Ieremia

et al. 2018

Growth Hormone & IGF Research

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“…Consistent with prior findings, we report decreased percent fat mass and increased total lean mass in bGH mice as compared to their WT counterparts. The general phenotype of bGH mice is consistent with previous findings (10, 13,15,18), and is largely explained by the alterations in metabolic regulation induced by increased GH/IGF-1 activity. In particular, the potent lipolytic and anti-lipogenic effects of GH are likely responsible for the dramatic reduction in WAT mass (15,18).…”

Section: Discussionsupporting

confidence: 90%

“…This coexistence of improved insulin sensitivity and obesity suggests a 'metabolically healthy' obese phenotype in these mice. Conversely, transgenic mice expressing the bovine GH gene (bGH) are characterized by increased IGF-1 levels, accelerated growth, increased lean body mass, decreased WAT mass, and a shortened lifespan (11)(12)(13). Generally, these mice suffer from a number of pathological changes in glucose and lipid metabolism, including hyperinsulinemia and impaired insulin sensitivity despite normal fasting blood glucose (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot–Specific Manner in Male Mice With Modified GH Action

et al. 2017

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Growth hormone (GH) is a determinant of glucose homeostasis and adipose tissue (AT) function. Using 7-month-old transgenic mice expressing the bovine growth hormone (bGH) gene and growth hormone receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression of proteins involved in the interrelated signaling pathways of GH, insulinlike growth factor 1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice. Glycated hemoglobin levels were reduced in bGH and GHR-/- mice, and bGH mice displayed impaired gluconeogenesis as judged by pyruvate tolerance testing. Serum IGF-1 was elevated by 90% in bGH mice, whereas IGF-1 and insulin were reduced by 97% and 61% in GHR-/- mice, respectively. Igf1 RNA was increased in subcutaneous, epididymal, retroperitoneal, and brown adipose tissue (BAT) depots in bGH mice (mean increase ± standard error of the mean in all five depots, 153% ± 27%) and decreased in all depots in GHR-/- mice (mean decrease, 62% ± 4%). IGF-1 receptor expression was decreased in all AT depots of bGH mice (mean decrease, 49% ± 6%) and increased in all AT depots of GHR-/- mice (mean increase, 94% ± 8%). Insulin receptor expression was reduced in retroperitoneal, mesenteric, and BAT depots in bGH mice (mean decrease in all depots, 56% ± 4%) and augmented in subcutaneous, retroperitoneal, mesenteric, and BAT depots in GHR-/- mice (mean increase: 51% ± 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner.

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“…A recent study by Brooks et al demonstrated that transgenic mice with excess GH action via expression of a bovine GH transgene had increased FGF-21 when compared to wild-type, suggesting that GH plays a role in increasing FGF21 in circulation (26). In humans, Lundberg et al similarly showed that circulating FGF21 levels increased with administration of excess GH (27).…”

Section: Discussionmentioning

confidence: 99%

“…The purpose of this investigation was to distinguish between two competing hypotheses regarding the interplay between GH, FGF21, and steatohepatitis. Given data that GH increases FGF21 (26–28) and that FGF21 administration ameliorates steatohepatitis, the first hypothesis is that FGF21 mediates tesamorelin-related reductions in liver fat, in which case we would expect an increase in FGF21 with liver fat reduction. Alternatively, if FGF21 is upregulated in the context of steatosis and steatohepatitis due to FGF21 resistance and/or compensatory mechanisms, the second hypothesis is that FGF21 would decrease with tesamorelin administration in association with improved markers of steatohepatitis (gamma glutamyl transpeptidase [GGT] and FIB4 index).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

Braun

Feldpausch

Czerwonka

et al. 2017

Growth Hormone & IGF Research

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Objective Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans. Methods 50 HIV-infected men and women with increased abdominal adiposity participated in this randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo daily for six months. Fasting laboratory measures, liver fat by 1H-magnetic resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly selected subset. Results At baseline, serum log10 FGF21 was significantly associated with log10 liver fat (r=0.32, p=0.03). Log10 FGF21 tended to decrease in the tesamorelin group compared to placebo (p=0.06). Among the entire cohort, reductions in FGF21 were significantly associated with reductions in liver fat (ρ=0.41, p=0.01), log10 gamma glutamyl tran speptidase (GGT, r=0.40, p=0.009), and FIB4 index (r=0.37, p=0.02). Conclusions In HIV-infected individuals, FGF21 is significantly positively associated with liver fat. FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve. Moreover, these data suggest that tesamorelin improves liver fat via pathways other than increasing serum FGF21.

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Fibroblast growth factor 21, fibroblast growth factor receptor 1, and β-Klotho expression in bovine growth hormone transgenic and growth hormone receptor knockout mice

Cited by 16 publications

References 56 publications

Growth hormone activated STAT5 is required for induction of beige fat in vivo

Growth hormone activated STAT5 is required for induction of beige fat in vivo

Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot–Specific Manner in Male Mice With Modified GH Action

Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

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