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Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle
Univ. Campus of Tafira, Las Palmas de Gran Canaria, Canary Islands, Spain; Research Institute of Biomedical and Health Sciences, Las Palmas de Gran Canaria, Spain.
Univ. Campus of Tafira, Las Palmas de Gran Canaria, Canary Islands, Spain.
Univ. Campus of Tafira, Las Palmas de Gran Canaria, Canary Islands, Spain.
Univ. Campus of Tafira, Las Palmas de Gran Canaria, Canary Islands, Spain.
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2017 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 123, no 5, p. 1276-1287Article in journal (Refereed) Published
Abstract [en]

In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt-1·day-1) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7; 0.8 g·kg body wt-1·day-1). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr1141, phospho-Tyr985OBR, JAK2, and phospho- Tyr1007/1008JKK2protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr705STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively (P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression (r-=0.75), phospho- Tyr985OBR (r = 0.88), and phospho-Tyr705STAT3/STAT3 (r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in response to a severe energy deficit, contributing to increase maximal fat oxidation. The responses are more prominent in the arm muscles than in the legs but partly blunted by whey protein ingestion and high volume of exercise. This occurs despite an increase of protein tyrosine phosphatase 1B protein expression, a known inhibitor of insulin and leptin signaling.

Place, publisher, year, edition, pages
2017. Vol. 123, no 5, p. 1276-1287
Keywords [en]
Energy balance, Leptin, Protein tyrosine phosphatase 1B, STAT3, Ultraendurance
National Category
Sport and Fitness Sciences
Identifiers
URN: urn:nbn:se:miun:diva-32351DOI: 10.1152/japplphysiol.00454.2017ISI: 000416597900029PubMedID: 28729389Scopus ID: 2-s2.0-85034115698OAI: oai:DiVA.org:miun-32351DiVA, id: diva2:1163960
Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-21Bibliographically approved

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Holmberg, Hans-Christer

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