In this edition:
Research from the Ntambi and Simcox Labs in the Department of Biochemistry reveals an enzyme’s important role in maintaining a healthy balance of lipids in our bodies. Here’s the run down on their latest research, published in the Journal of Lipid Research:
- Cellular function relies in part on a healthy balance of fat molecules called lipids, which are regulated by enzymes.
- Deficiency and overabundance of certain lipids can result in metabolic diseases.
- Researchers in the Ntambi and Simcox Labs studied SCD1, an enzyme responsible for regulating some lipids. They found that SCD1 impacts the balance of lipids beyond those it makes and regulates directly.
What background information do you need to know?
Healthy functioning of cells relies on a carefully balanced array of lipids, or fat molecules. Lipids store energy, help to form cell membranes, signal to other molecules, and more. Enzymes such as stearoyl-CoA desaturase-1 (SCD1) help regulate the balance of lipids in a cell, in part by synthesizing molecules such as oleic acid — a lipid found in foods such as olive oil, canola oil, and chicken fat.
When a cell’s composition of lipids is out of balance, it can lead to increased cellular storage of lipids that drive metabolic disorders such as diabetes. A kind of analysis called lipidomics provides an assessment of lipids in a biological sample using a mass spectrometer (a tool used to identify the the types and quantities of different molecules in a biological sample, including blood and liver). More robust data on the implications of high and low levels of lipids may provide helpful information about a person’s susceptibility to disease, but the functional implications of lipid composition is not entirely understood by scientists and medical professionals.
Why is it complicated to understand how lipids impact health?
Researchers are still learning about the delicate interplay among different lipid compositions and disease. Often, diseases may result from either elevated or diminished levels of lipids. For example, elevated levels of SCD1 (which contribute to higher levels of the lipids it produces) can be associated with metabolic dysfunctions associated with obesity, cancer, and insulin resistance. While a deficiency in the enzyme may protect against these diseases, it is also associated with metabolic stress and an unhealthy build-up of fats in the blood vessels (atherosclerosis).
How have scientists made progress?
Researchers in the Ntambi and Simcox Labs were interested in learning more about how SCD1 impacts lipid composition in liver cells. The team studied the livers of mice that were bred without the expression of SCD1, focusing on metabolically significant saturated and unsaturated lipids.
Their findings, obtained using lipidomics, indicate that the absence of SCD1 results in a decrease of energy storage lipids, such as triglycerides, and an overproduction of some metabolically significant saturated lipids. Among the overproduced lipids is acylcarnitine, a lipid known to induce insulin resistance, which can lead to diabetes. These findings are consistent with previous studies from the Ntambi Lab indicating that, in mice, the loss of SCD1 protects against obesity and prevents the onset of diabetes.
Ultimately, the absence of SCD1 resulted in changes to the abundance of lipids beyond those regulated directly by SCD1. Supplementing the mice’s diets with SCD1-synthesized oleic acid restored the lipid balance, suggesting that diet could play a role in regulating lipid composition. The research supports a new understanding of SCD1 as playing a critical role regulating cells’ lipid balance, expanding its known function beyond production of oleic acid and revealing details of the connection between SCD1 and metabolic disease.
Written by Renata Solan.
In Research In Brief: The What, Why, and How, we explore new research from the UW–Madison Department of Biochemistry to learn more about the world around us — and inside us.
This edition of Research in Brief: The What, Why, and How is based on the following publication: Kalyesubula, Von Bank, Davidson, Burhans, Becker, Alijohani, Simcox, and Ntambi. Stearoyl-CoA desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines. Journal of Lipid Research, May 2025, 9:100824. This research was funded in part by the National Institutes of Health/National Institute of Digestive and Kidney Disease (R01DK118093 and R01DK133479), the Glenn Foundation and American Foundation for Aging Research (A22068), BreakThroughT1D (JDRF201309442), and the National Science Foundation Graduate Research Fellowship Program (DGE-1747503. Judith Simcox is an HHMI Freeman Hrabowski Scholar.