A new study by Case Western Reserve researchers, published in the journal Nature Communications, has linked a single protein to the metabolism of sugars, fats and proteins affecting cellular energy production. The protein called KLF15 (Kruppel-like Factor 15) keeps the body in metabolic balance; and burns fat during exercise and regulates the heart’s contractile and electrical activity.
“It’s important to understand how nutrients are acquired, how they are made available to tissues, how they are used, and how disease alters the dynamics of the process,” said Mukesh K. Jain, MD, Ellery Sedgwick Jr. Chair; Distinguished Scientist and director of the Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine. “The heart, for example, is a very energy-demanding organ that succumbs to failure if it has insufficient access to nutrients or fails to properly utilize nutrients.”
“The beautiful aspect of this work is that nature designed this very clever molecule to regulate both nutrient availability and use, and the molecule functions broadly across all nutrient classes, which is very exciting. That’s what makes it an important discovery,” said Jain, also the scientific director of the Harrington Discovery Institute, chief research officer of the Harrington Heart & Vascular Institute, and chief scientific officer of University Hospitals Health System.
The researchers used a mouse model deficient in the KLF15 protein and concentrated on KLF15 with regard to bile acids. KLF15-deficient mice produced 40 to 50 percent less bile acid than normal mice, making them less capable of absorbing the lipids and the nutrients they contained. The pathways involved in bile acid elimination are the same used for appropriate metabolism of many drugs.
“If Drs. Han and Zhang’s hypothesis is right, then additional insights into the KLF15 pathway may not only help prevent diseases affected by bile acid amounts, but it could have major implications for drug metabolism,” Jain said. “That’s a future direction.”
Joining Han, Zhang, and Jain in this research were contributing authors Hong Shi, Lilei Zhang, Guangjin Zhou, Panjamaporn Sangwung, Derin Tugal, G. Brandon Atkins, Domenick A. Prosdocimo, Yuan Lu, and Xudong Liao, all of Case Western Reserve; Rajan Jain and Jonathan A. Epstein, both of the University of Pennsylvania; Xiaonan Han, Cincinnati Children’s Hospital Medical Center; and Patrick Tso, University of Cincinnati College of Medicine.