Discovery and characterization of a novel peptide regulating energy homeostasis

Ngo, Thi My Hanh (2026): Discovery and characterization of a novel peptide regulating energy homeostasis. Dissertation, LMU München: Faculty of Medicine

Abstract

Obesity is a multifaceted, chronic disease characterized by the accumulation of excessive fat deposits, which can disrupt endocrine function and contribute to various health issues, such as type 2 diabetes, cardiovascular diseases, cancers, and musculoskeletal disorders. The prevalence of obesity is projected to affect over 1.2 billion individuals by 2030, reaching pandemic proportions. The identification of hormone glucagon-like peptide 1 (GLP-1) as a pivotal regulator of food intake and energy homeostasis has paved the way for the development of the first generation of anti-obesity therapies. Nevertheless, GLP-1 based therapies are often result in gastrointestinal side effects highlighting the need to explore novel therapeutic targets and alternative mechanisms to regulate energy balance and homeostasis. My PhD work focuses on the role of SP16, a synthetic peptide derived from endogenous serpin derived peptide that is newly associated to obesity. The main objective of my study is to explore the metabolic regulation of SP16 on adipocytes. I found that SP16 promotes cAMP-dependent lipolysis through the activation of the glucose-dependent insulinotropic polypeptide receptor (GIPR). SP16 was also able to increase mitochondrial oxygen consumption and upregulates thermogenic marker expression. Interestingly, I have also observed that high concentration of SP16 antagonizes the insulin signaling pathway in adipocytes, leading to a reduction in mRNA lipogenesis markers. In vivo data supports my in vitro findings. Acute SP16 treatment promotes the plasma free fatty acid (FFA) and FFA release in epididymal white adipose tissue (eWAT) of mice fed with high fat diet (HFD). Additionally, acute treatment with SP16 significantly improves glucose tolerance, phosphorylated AKT level in eWAT and plasma leptin level (Figure 1). In conclusion, my findings highlight the potential of SP16 as the base to develop novel peptides and as effective tool for tackling obesity. Additional experiments are required to thoroughly explore the metabolic advantages offered by SP16.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Peptide, SP16, obesity, GIPR, Insulin receptor
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 24. March 2026
• 1. Referee: Bartelt, Alexander
• Signature of the printed copy: 0700/UMD 22756