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Adipocyte Leptin Signaling Regulates Glycemia and Cardiovascular Function by Enhancing Brown Adipose Tissue Thermogenesis in Obese Male Mice.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Adipocyte Leptin Signaling Regulates Glycemia and Cardiovascular Function by Enhancing Brown Adipose Tissue Thermogenesis in Obese Male Mice.
Συγγραφείς: Ono Y; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA., Kennard S; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA., Wall BT; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA., Ma J; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA., Belin de Chantemèle EJ; Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA.; Division of Cardiology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA.
Πηγή: Diabetes [Diabetes] 2026 Mar 01; Vol. 75 (3), pp. 441-453.
Τύπος έκδοσης: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
Imprint Name(s): Publication: Alexandria, VA : American Diabetes Association
Original Publication: [New York, American Diabetes Association]
Ιατρικοί όροι (MeSH): Adipose Tissue, Brown*/metabolism , Leptin*/metabolism , Thermogenesis*/physiology , Obesity*/metabolism , Adipocytes*/metabolism , Blood Glucose*/metabolism, Receptors, Leptin/metabolism ; Receptors, Leptin/genetics ; Signal Transduction/physiology ; Energy Metabolism/physiology ; Animals ; Male ; Mice ; Mice, Knockout ; Female ; Mice, Obese
Περίληψη: Although control of metabolism by leptin is primarily viewed as centrally mediated, leptin has also been shown to directly regulate adipocyte function. However, the impact of the peripheral effects of leptin on systemic metabolism, especially in the context of obesity, remains unclear. To address this question, we selectively restored adipocyte leptin receptor (LEPR) expression in obese male and female LEPR-conditional knockout mice. Adipocyte LEPR restoration did not affect body weight but selectively increased brown adipose tissue (BAT) mass in male mice. This was associated with increased energy expenditure, smaller BAT adipocytes, lower triglycerides content, and increased markers of browning and lipolysis exclusively in males. Additionally, adipocyte LEPR restoration enhanced the expression of markers of endothelial cells and angiogenesis in male mouse BAT, supporting increased local vascularization. Improved BAT function in males was also associated with lower HbA1c, better insulin sensitivity, reduced systolic blood pressure, decreased arterial stiffness, and improved endothelial function. Lastly, adipocyte LEPR restoration lowered circulating proinflammatory cytokines and reduced tissue inflammation in the aorta and heart, again in males only. These findings reveal a critical role for adipocyte leptin signaling in regulating BAT function and emphasize its importance in maintaining glycemic and cardiovascular health in males with obesity.
Article Highlights: Leptin is known to enhance brown adipose tissue (BAT) activity through sympathetic stimulation. However, in vitro studies suggest leptin could also act directly on adipocytes to promote lipolysis. Whether these peripheral effects of leptin are relevant to systemic metabolic control in obesity remains unclear. We addressed this question by selectively restoring leptin receptor (LEPR) expression in adipocytes of obese LEPR-conditional knockout mice. LEPR restoration selectively enhanced BAT activity in male mice, which led to improved glycemic control and cardiovascular function. These findings reveal a crucial role for BAT leptin signaling in regulating energy expenditure and glycemic and cardiovascular health, primarily in males.
(© 2026 by the American Diabetes Association.)
Σχόλια: Update of: bioRxiv. 2025 Oct 11:2025.10.10.681380. doi: 10.1101/2025.10.10.681380.. (PMID: 41279632)
References: Cell. 2015 Sep 24;163(1):84-94. (PMID: 26406372)
Mol Med Rep. 2020 Feb;21(2):945-952. (PMID: 31789415)
Cell Res. 2009 Jan;19(1):116-27. (PMID: 19114994)
Clin Sci (Lond). 1993 Nov;85(5):563-8. (PMID: 8287644)
J Neurosci. 2011 Aug 24;31(34):12189-97. (PMID: 21865462)
PPAR Res. 2013;2013:476049. (PMID: 23554809)
Endocrinology. 2009 Sep;150(9):4124-34. (PMID: 19477937)
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8033-8. (PMID: 10884431)
Am J Physiol Regul Integr Comp Physiol. 2017 Jun 1;312(6):R938-R947. (PMID: 28356295)
Sci Rep. 2019 Mar 1;9(1):3307. (PMID: 30824713)
Eur J Med Res. 2010 Nov 4;15 Suppl 2:50-4. (PMID: 21147620)
J Clin Med. 2024 Mar 28;13(7):. (PMID: 38610736)
Hypertension. 2019 Dec;74(6):1399-1408. (PMID: 31656096)
Front Endocrinol (Lausanne). 2019 Dec 13;10:841. (PMID: 31920961)
Curr Pharm Des. 2013;19(10):1956-64. (PMID: 23305268)
Diabetes. 2017 Feb;66(2):392-406. (PMID: 28108608)
Int J Mol Sci. 2024 Mar 14;25(6):. (PMID: 38542288)
Nat Rev Mol Cell Biol. 2005 Mar;6(3):248-61. (PMID: 15738989)
J Clin Invest. 2014 May;124(5):2099-112. (PMID: 24713652)
Mol Nutr Food Res. 2016 Jan;60(1):18-42. (PMID: 26201764)
Clin Sci (Lond). 2016 Jun 1;130(11):881-93. (PMID: 26935109)
Int J Mol Sci. 2020 Nov 18;21(22):. (PMID: 33217955)
Cell Metab. 2014 Jul 1;20(1):103-18. (PMID: 24930973)
Horm Res. 2002;58(2):88-93. (PMID: 12207168)
Eur J Pharmacol. 2022 Jul 5;926:175040. (PMID: 35598846)
Front Physiol. 2021 Feb 09;11:624903. (PMID: 33633579)
Int J Mol Sci. 2021 Feb 03;22(4):. (PMID: 33546400)
Biochim Biophys Acta. 2014 Mar;1842(3):414-23. (PMID: 23685313)
J Mol Med (Berl). 2013 Mar;91(3):323-8. (PMID: 23430240)
Nature. 2002 Jan 17;415(6869):339-43. (PMID: 11797013)
Nat Rev Cardiol. 2023 Oct;20(10):685-695. (PMID: 37193856)
J Clin Invest. 2007 Sep;117(9):2362-8. (PMID: 17786229)
Circulation. 2025 Apr 22;151(16):1187-1203. (PMID: 39907014)
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1160-1171. (PMID: 29409985)
J Biol Chem. 2001 Mar 16;276(11):7697-700. (PMID: 11152449)
Biochem Biophys Res Commun. 1997 Nov 26;240(3):590-4. (PMID: 9398609)
Physiol Rev. 2004 Jan;84(1):277-359. (PMID: 14715917)
Curr Hypertens Rep. 2018 Sep 18;20(11):96. (PMID: 30229358)
Front Physiol. 2023 Jan 10;13:1106380. (PMID: 36703934)
Cell Metab. 2014 Jun 3;19(6):1058-65. (PMID: 24768298)
HPB (Oxford). 2011 Apr;13(4):225-33. (PMID: 21418127)
J Clin Invest. 2006 Mar;116(3):615-22. (PMID: 16511594)
J Endocrinol. 2002 Dec;175(3):735-44. (PMID: 12475384)
Pharmacol Res. 2015 Dec;102:235-44. (PMID: 26523876)
Nature. 1994 Dec 1;372(6505):425-32. (PMID: 7984236)
Australas J Dermatol. 2013 Nov;54(4):259-63. (PMID: 24164178)
Curr Obes Rep. 2017 Dec;6(4):389-396. (PMID: 29101739)
Diabetes. 2004 Sep;53(9):2443-8. (PMID: 15331557)
World J Diabetes. 2015 May 15;6(4):548-53. (PMID: 25987952)
Biochem Biophys Res Commun. 2020 Oct 20;531(3):297-304. (PMID: 32800538)
PLoS One. 2012;7(7):e40650. (PMID: 22808220)
Diabetes. 2007 Dec;56(12):2910-8. (PMID: 17848624)
Nat Med. 1996 May;2(5):585-9. (PMID: 8616721)
Front Endocrinol (Lausanne). 2021 Apr 13;12:652444. (PMID: 33927694)
Clin Nutr. 1999 Oct;18(5):269-74. (PMID: 10601533)
Sci Transl Med. 2020 Aug 5;12(555):. (PMID: 32759275)
Signal Transduct Target Ther. 2023 Apr 10;8(1):152. (PMID: 37037849)
Nat Rev Endocrinol. 2014 Jan;10(1):24-36. (PMID: 24146030)
Grant Information: R01 HL175471 United States HL NHLBI NIH HHS; R01HL176323 United States HL NHLBI NIH HHS; R01 HL147639 United States HL NHLBI NIH HHS; R01AR08230 United States AR NIAMS NIH HHS; R01 HL155265 United States HL NHLBI NIH HHS; P01HL1605571 United States HL NHLBI NIH HHS; R01 HL176323 United States HL NHLBI NIH HHS; 25POST136864 American Heart Association; R01HL155265 United States HL NHLBI NIH HHS; R01HL175471 United States HL NHLBI NIH HHS
Substance Nomenclature: 0 (Leptin)
0 (Receptors, Leptin)
0 (Blood Glucose)
0 (leptin receptor, mouse)
Entry Date(s): Date Created: 20260106 Date Completed: 20260220 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC12928713
DOI: 10.2337/db25-0388
PMID: 41490102
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1939-327X
DOI:10.2337/db25-0388