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Leptin, Acting at Central Level, Increases FGF21 Expression in White Adipose Tissue via PPARβ/δ.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Apr 28; Vol. 22 (9). Date of Electronic Publication: 2021 Apr 28. - Publication Year :
- 2021
-
Abstract
- The altered function of adipose tissue can result in obesity, insulin resistance, and its metabolic complications. Leptin, acting on the central nervous system, modifies the composition and function of adipose tissue. To date, the molecular changes that occur in epididymal white adipose tissue (eWAT) during chronic leptin treatment are not fully understood. Herein we aimed to address whether PPARβ/δ could mediate the metabolic actions induced by leptin in eWAT. To this end, male 3-month-old Wistar rats, infused intracerebroventricularly (icv) with leptin (0.2 μg/day) for 7 days, were daily co-treated intraperitoneally (ip) without or with the specific PPARβ/δ receptor antagonist GSK0660 (1 mg/kg/day). In parallel, we also administered GSK0660 to control rats fed ad libitum without leptin infusion. Leptin, acting at central level, prevented the starvation-induced increase in circulating levels of FGF21, while induced markedly the endogenous expression of FGF21 and browning markers of eWAT. Interestingly, GSK0660 abolished the anorectic effects induced by icv leptin leading to increased visceral fat mass and reduced browning capacity. In addition, the pharmacological inhibition of PPARβ/δ alters the immunomodulatory actions of central leptin on eWAT. In summary, our results demonstrate that PPARβ/δ is involved in the up-regulation of FGF21 expression induced by leptin in visceral adipose tissue.
- Subjects :
- Animals
Hypothalamus metabolism
Infusions, Intraventricular
Klotho Proteins
Male
Membrane Proteins metabolism
PPAR gamma antagonists & inhibitors
PPAR-beta antagonists & inhibitors
Rats, Wistar
Sulfones
Thiophenes
Rats
Adipose Tissue, White physiology
Fibroblast Growth Factors metabolism
Leptin physiology
PPAR gamma metabolism
PPAR-beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33924880
- Full Text :
- https://doi.org/10.3390/ijms22094624