2. Academic Validation
  3. Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

  • Sci Rep. 2020 Jul 30;10(1):12785. doi: 10.1038/s41598-020-69634-3.
Jiani Wang 1 2,  Christina Ortiz 1,  Lindsey Fontenot 1,  Riya Mukhopadhyay 1,  Ying Xie 1 2,  Ivy Ka Man Law 1,  David Q Shih 3,  S Anjani Mattai 4,  Zhaoping Li 5,  Hon Wai Koon 6
Affiliations

Affiliations

  • 1 Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Room 44-129, Center for Health Sciences Building, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA.
  • 2 Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China.
  • 3 F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • 4 Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • 5 Division of Clinical Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • 6 Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Room 44-129, Center for Health Sciences Building, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. [email protected].
PMID: 32733043 DOI: 10.1038/s41598-020-69634-3
Abstract

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum Leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue Leptin mRNA expression in HFD-treated recipient mice. Elafin improved Leptin sensitivity via reduced interferon-gamma expression and induced adipose Leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates Leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

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