Academic Journal
Leptin mediates the effects of sulfur amino acid restriction on food intake and body weight in mice.
| Title: | Leptin mediates the effects of sulfur amino acid restriction on food intake and body weight in mice. |
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| Authors: | Cooke D; Orentreich Foundation for the Advancement of Science, Inc., Cold Spring, New York, USA., Ouattara A; Orentreich Foundation for the Advancement of Science, Inc., Cold Spring, New York, USA., Ables GP; Orentreich Foundation for the Advancement of Science, Inc., Cold Spring, New York, USA. Electronic address: gables@orentreich.org. |
| Source: | The Journal of nutritional biochemistry [J Nutr Biochem] 2026 Oct; Vol. 156, pp. 110396. Date of Electronic Publication: 2026 May 05. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE |
| Imprint Name(s): | Publication: <1996->: New York, NY : Elsevier Science Original Publication: Stoneham, MA, USA : Butterworths, c1990- |
| MeSH Terms: | Leptin*/metabolism , Leptin*/blood , Leptin*/genetics , Amino Acids, Sulfur*/deficiency , Eating* , Body Weight*, Hypothalamus/metabolism ; Obesity/metabolism ; Obesity/etiology ; Receptors, Leptin/genetics ; Receptors, Leptin/metabolism ; Uncoupling Protein 1/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Male ; Mice ; Iodothyronine Deiodinase Type II ; Mice, Inbred C57BL ; Mice, Obese ; Weight Loss |
| Abstract: | Sulfur amino acid restriction (SAAR) paradoxically increases food intake while inducing weight loss, but the mechanisms underlying these outcomes remain unclear. To investigate the role of leptin in this response, we assessed food intake, body weight, and metabolic markers in diet-induced obese (DIO), leptin-deficient (ob/ob), and leptin receptor-deficient (db/db) mice. In DIO-SAAR mice, increased food intake was associated with hypothalamic upregulation of orexigenic (Agrp, Npy, and Mchr1) and downregulation of anorexigenic (Pomc, Cartpt, and Bdnf) mRNA levels. This orexigenic profile is accompanied by reduced adiposity and lower circulating leptin levels, suggesting that decreased leptin may induce compensatory increased food intake. Despite increased food intake, SAAR also induces weight loss, which is associated with enhanced β3-adrenergic signaling in brown and inguinal white AT (BAT and iWAT), as reflected by elevated Adrb3 and Ucp1 mRNA levels but downregulated protein expression, suggesting post-transcriptional regulation. These phenotypes induced by SAAR may possibly involve thyroid hormone metabolism, as indicated by increased circulating T3 and T4 concentrations and upregulation of BAT deiodinase 2 (D2) mRNA. Importantly, these metabolic effects of SAAR are attenuated in ob/ob and abolished in db/db mice, despite reductions in circulating SAA levels. Furthermore, leptin treatment during SAAR reduced food intake, induced weight loss, demonstrating preserved leptin sensitivity in low fat diet-fed and ob/ob mice. These findings reveal that leptin is required for both increased food intake and weight loss during SAAR. (Copyright © 2026 Orentreich Foundation for the Advancement of Science, Inc. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Brown adipose tissue; Hypothalamus; Leptin; Sulfur amino acid restriction |
| Substance Nomenclature: | 0 (Leptin) 0 (Amino Acids, Sulfur) 0 (Receptors, Leptin) EC 1.11.1.- (Iodothyronine Deiodinase Type II) 0 (Uncoupling Protein 1) 0 (Ucp1 protein, mouse) |
| Entry Date(s): | Date Created: 20260507 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260615 |
| DOI: | 10.1016/j.jnutbio.2026.110396 |
| PMID: | 42097465 |
| Database: | MEDLINE |
| ISSN: | 1873-4847 |
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| DOI: | 10.1016/j.jnutbio.2026.110396 |