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Michael Rudolph, PhD

Early-Life Fatty Acid Exposures Dictate Obesity Predisposition

Mike Rudolph

Background About the Women’s Health Problem: My Women’s Health research investigates how maternal overweight and obesity, through the quality of dietary fats they consume, affect the risk of overweight and obesity of the baby.  The nutrients provided to the baby through breastmilk are thought to protect against this risk by establishing lasting benefits to metabolism. The idea that poor quality fats in the mother’s diet might have lasting effects on infant metabolism was recognized over 40 years ago, now called the ‘Developmental Origins of Metabolic Disease.’ Since that time, obesity has doubled in children and quadrupled in adolescents, as high-quality fats in the maternal diet have been replaced by less diverse vegetable oils introduced by processed foods that are calorie dense and nutrient poor. The principle tissue transformed by dietary fats during overeating is the adipose (fat tissue). In infants, adipose normally grows rapidly after birth. It responds directly to the fats contained in the mother’s breastmilk that originate directly from mother’s dietary fat.  Because the quality of fats provided in the maternal diet can be changed, this opens a wonderful opportunity for intervention against childhood obesity risk, and to improve the health of the mother. 

Approach to Investigate the Problem: This research uses cutting edge technology to isolate stem cells from fat tissue of mouse pups exposed to high- and low-quality fats. I have generated a mouse model to identify the specific genes in fat tissue stem cells stimulated by high- and low-quality fats during adipose growth in the young.  This model is used in combination with maternal obesity to study how milk production and milk composition are changed by mother’s health difficulties, such as insulin resistance. The idea is that the adipocyte stem cells in the pups will harbor permanent changes established by the amounts and quality of fats early in life, which will control the way the cells divide and grow. These stem cells will then give rise to mature adipocytes (fat cells) that are pre-conditioned with beneficial or unhealthy responses to overeating later in life. 

Importance to Women’s Health: I will use clinical observations from the mothers and their infants enrolled in our collaborative study to guide the questions I can answer using the mouse. Ultimately, I wish identify genes that establish a predisposition for obesity early in life to develop therapies that prime the baby with lasting protection against obesity later in life.  By understanding the fats comprised in mother’s milk and how maternal obesity influences milk, we can recommend the kinds of the fats she consumes to produce breastmilk that is optimized to safeguard against future metabolic diseases.