Vol.:(0123456789) 1 3 Infammation Research (2020) 69:1019–1026 https://doi.org/10.1007/s00011-020-01383-5 ORIGINAL RESEARCH PAPER Ghrelin‑induced multi‑organ damage in mice fed obesogenic diet Carole Dagher‑Hamalian 1  · Joseph Stephan 1  · Nadine Zeeni 2  · Zeina Harhous 1  · Wassim N. Shebaby 2  · Maya S. Abdallah 1  · Wissam H. Faour 1 Received: 8 May 2020 / Revised: 13 July 2020 / Accepted: 16 July 2020 / Published online: 27 July 2020 © Springer Nature Switzerland AG 2020 Abstract Objective and design Ghrelin has a key role in modulating energy metabolism and weight gain. The present study aimed at studying the potential role of ghrelin in the development and/or exacerbation of organ damage in a mouse model of diet- induced obesity. Objective and design Adult mice were fed one of two diets for 20 weeks: standard high carbohydrate (HC) or high-fat high- sugar (HFHS). Starting week 17, the animals were given regular intraperitoneal ghrelin (160 µg/kg) or saline injections Abdominal fat, serum creatinine, and glucose levels, as well as kidney, liver and heart weight and pathology were assessed. Results Ghrelin-injected mice showed signifcant organ damage, which was more exacerbated in HFHS-fed animals. While the HFHS diet was associated with signifcant liver damage, ghrelin administration did not reverse it. Interestingly, ghrelin administration induced moderate kidney damage and signifcantly afected the heart by increasing perivascular and myocar- dium fbrosis, steatosis as well as infammation. Moreover, serum creatinine levels were higher in the animal group injected with ghrelin. Conclusion Ghrelin administration was associated with increased functional and structural organ damage, regardless of diet. The present study provides novel evidence of multi-organ physiologic alterations secondary to ghrelin administration. Keywords Ghrelin · Nephropathy · Obesity · Cardiomyopathy · Hepatopathology Introduction Increased food intake, reduced satiety and dysregulation of energy metabolism contribute to the onset and maintenance of obesity. Specifcally, ghrelin, an orexigenic peptide hor- mone, may play a key role in modulating the response to satiety in the context of obesity or obesogenic diets [1]. While secretion levels of most gut hormones are increased with food intake and decreased with fasting, ghrelin secre- tion and plasma levels decrease with food intake and peak right before meals, achieving sufcient concentrations to stimulate hunger feeling and food intake [1, 2]. In the context of obesity, previous studies have indicated that ghrelin levels are reduced in obese individuals and in subjects with insulin resistance [3, 4]. Additionally, it was previously reported that elevated glucose and lipids levels participate in reducing ghrelin secretion under conditions of high fat—high sucrose diet [5]. In the same line of evidence, a study that aimed to investigate the efect of a high-fat diet on plasma ghrelin and leptin levels has reported that long-term intake of a high- fat diet caused hyperleptinemia and hypoghrelinemia [6]. Overall, it seems that under conditions of high-fat high-sugar diets and obesity, ghrelin levels are reduced. Ghrelin was also found to inhibit glucose-mediated secretion of insulin in animals and humans [ 7 ]. It was shown that ghrelin can modulate insulin level through stimulating the release of four hormones known to antagonize insulin action including glucagon [8], growth Inflammation Research Responsible Editor: John Di Battista. Carole Dagher-Hamalian and Joseph Stephan have contributed equally to this work. * Wissam H. Faour wissam.faour@lau.edu.lb 1 Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, PO Box 36, Byblos, Lebanon 2 Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, PO Box 36, Byblos, Lebanon