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Nicole Brooks Thesis Final.pdf (1.02 MB)

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Fibroblast Growth Factor 21 Expression in Mice with Altered Growth Hormone Action: Links to Obesity, Type 2 Diabetes Mellitus, and Increased Longevity

Brooks, Nicole E
http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461161246

Abstract Details

2016, Bachelor of Science (BS), Ohio University, Biological Sciences.
Objective: Although growth hormone (GH) and fibroblast growth factor 21 (FGF21) have a reported relationship, FGF21 and its receptor fibroblast growth factor 1 (FGFR1) and cofactor ß-Klotho (KLB) have not been analyzed in states of altered GH action. This study measured circulating FGF21 and tissue expression of Fgf21, Fgfr1, and Klb in mice with modified GH action to further elucidate the regulation of FGF21 action by GH. Design: 7 month old male mice bovine GH transgenic (bGH) mice (n = 9) and wild type (WT) controls (n = 10), and GH receptor knockout (GHR-/-) mice (n = 8) and WT controls (n = 8) were used for all measurements. Body composition was performed before dissection and tissue weights were measured at the time of dissection. Serum FGF21 levels were evaluated by ELISA. Expression of Fgf21, Fgfr1, and Klb mRNA in white adipose tissue (AT), brown AT, and liver were evaluated by real-time quantitative PCR. Results: As expected, bGH mice had increased body weight (p = 3.70E-8), but decreased percent fat mass (p = 4.87E-4). Likewise, GHR-/- mice had decreased body weight (p = 1.78E-10), but increased percent fat mass (p = 1.52E-9), due to increased size of the subcutaneous AT depot when normalized to body weight (p = 1.60E-10). Serum FGF21 levels were significantly elevated in bGH mice (p = 0.041) and unchanged in GHR-/- mice (p = 0.88). Expression of Fgf21, Fgfr1, and Klb mRNA in white AT and liver were downregulated or unchanged in both bGH and GHR-/- mice. The only exception was Fgf21 expression in brown AT of GHR-/-, which trended toward increased expression (p = 0.075). Conclusion: We provide evidence that circulating FGF21 is increased in bGH animals, but remains unchanged in GHR-/- mice. Downregulation or no change in Fgf21, Fgfr1, and Klb expression are seen in white AT, brown AT, and liver of bGH and GHR-/- mice when compared to their respective controls, except for an increase in brown AT Fgf21 expression in GHR-/- mice, which could suggest a possible link to increased thermogenic potential in these mice. Overall, these results suggest modulation of FGF21 action by GH, and possible FGF21 resistance in both bGH and GHR-/- animals. Mice with altered GH action are of value to study further to better understand the regulation and interplay between GH action and FGF21 expression.
Darlene Berryman, PhD (Advisor)
Soichi Tanda, PhD (Advisor)
82 p.
Biology; Biomedical Research; Molecular Biology
FGF21; fibroblast growth factor 21; Fgfr1; fibroblast growth factor receptor 1; Klb; beta klotho; GH; growth hormone; FGF21 resistance; AT; adipose tissue; liver; brown adipose tissue; white adipose tissue

Recommended Citations

Citations

  • Brooks, N. E. (2016). Fibroblast Growth Factor 21 Expression in Mice with Altered Growth Hormone Action: Links to Obesity, Type 2 Diabetes Mellitus, and Increased Longevity [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461161246

    APA Style (7th edition)

  • Brooks, Nicole. Fibroblast Growth Factor 21 Expression in Mice with Altered Growth Hormone Action: Links to Obesity, Type 2 Diabetes Mellitus, and Increased Longevity . 2016. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461161246.

    MLA Style (8th edition)

  • Brooks, Nicole. "Fibroblast Growth Factor 21 Expression in Mice with Altered Growth Hormone Action: Links to Obesity, Type 2 Diabetes Mellitus, and Increased Longevity ." Undergraduate thesis, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461161246

    Chicago Manual of Style (17th edition)

ouhonors1461161246
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This open access ETD is published by Ohio University Honors Tutorial College and OhioLINK.