Metabolism

The obesity rate has more than doubled in the last 30 years, affecting more than one billion people worldwide. Current treatment options include lifestyle interventions, bariatric surgery, and GLP-1 drugs like Ozempic or Wegovy, but many patients struggle to access or complete these treatments or to maintain their weight loss afterward.

Salk scientist Alan Saghatelian, PhD, postdoctoral researcher Victor Pai, PhD, and colleagues are paving the way for new treatment strategies by exploring the link between obesity and microproteins, a mysterious class of molecules found throughout the body. In a new study, the researchers screened thousands of fat cell genes using CRISPR gene editing tools and found dozens of genes that likely code for microproteins involved in regulating fat cell development or lipid accumulation. The findings identify new microproteins that could serve as potential drug targets for treating obesity and other metabolic disorders. The study also showcases the value of CRISPR screening in future microprotein discovery.

Like bees breathing life into gardens, providing pollen and making flowers bloom, little cellular machines called mitochondria breathe life into our bodies, buzzing with energy as they produce the fuel that powers each of our cells.

Maintaining mitochondrial metabolism requires input from many molecules and proteins, some of which have yet to be discovered. Salk scientist Alan Saghatelian, PhD, postdoctoral researcher Andréa Rocha, PhD, and colleagues are taking a closer look at whether mitochondria rely on microproteins—small proteins that have been difficult to find and, consequently, underestimated for their role in health and disease. In their new study, a microprotein discovered just last year at Salk, called SLC35A4-MP, was found to play a critical role in upholding mitochondrial structure and regulating metabolic stress in mouse fat cells. The findings plant the seed for future microprotein-based treatments for obesity, aging, and other mitochondrial disorders.