Research Description

Dr. Rudolph’s research investigates human infant fatty acid exposures, maternal obesity, maternal fatty acid intake, and their combined impact on infant body fat accumulation, and he studies developmental adipogenesis. His objectives are to understand 1.) how fatty acids - presented via mother’s milk – control adipogenic potential in her baby, and 2.) what fatty acid-derived molecular mechanisms protect against excessive infant adipose deposition.

As a Ludeman Family Center for Women's Health Research researcher, Dr. Rudolph studied how maternal obesity or poor diet can affect normal development in ways that predispose offspring for greater obesity risk.

BIRCWH project title: Early Life Fatty Acid Exposures Dictate Obesity Predisposition

Current research focus: I investigate how maternal derived fatty acids, especially from obese mothers, condition neonatal adipogenesis and future obesity risk. My lab has developed several novel methods to elucidate the cellular and molecular diversity of adipocyte stem-like cells in mice. Through customized flow cytometry, bulk and single cell RNA-sequencing, and lipid mass spectometry, we are beginning to understand the molecular and cellular cues that control developmental patterning of adipose tissue stem-like cells early in life. This includes the potential for differentiation and subtype heterogeneity, particularly during postnatal fat depot growth when metabolic programming is greatly influences by infant dietary nutrients.

How Dr. Rudolph became interested in this work: My dissertation focus was the molecular regulation of lipogenesis in lactating mammary epithelium, when I studied transgenic and genomic knockout mice to test important molecules regulating this process. During my T32 with the Perinatal Research Center, I began to shift my focus towards the consequences of altered milk fat composition on offspring development and how maternal obesity and diabetes might affect milk derived lipids. Using lipid mass spectrometry quantification of bioactive fatty acid exposure to the infant the greater the fat mass accumulation.About this time, my wife and I were expecting the birth of my son, which provided great meaning and motivation for the work and the research program I have developed. 

Clinical significance of this research: It has been known for 40 years that nutritional exposures, derived from maternal diet and presented to the offspring during fetal and infant development, can exert long-lasting effects on metabolism to affect disease risks later in life. About 1 in 5 children are overweight or obese, with recent predictions suggesting half of childhood obesity will occur by age 5 and the majority (>55%) of existing children will eventually become obese by 35-years old. Shockingly, ~30% of obese children now develop NAFLD. Importantly, the rise in childhood obesity mirrors the rates of maternal obesity (~40%), strongly supporting the role for perinatal exposures as establishing key factors of future metabolic diseases. In conjunction with several clinical collaborations, I leverage ongoing studies of maternal obesity and human infant adipogenesis to quantify milk fat quality and the composition of maternal fatty acid intake. In this way, I build a strong bride between basic and clinical research by connecting clinical studies with mechanistic studies in mouse models.

Relevance of this work to women's health or sex/gender differences: My research directly applies to women's health by investigating the relationships among maternal metabolic health, maternal diet, and the ways that offspring pattern fat depots during development. Importantly, we have observed that female relative to male infants have a greater % body fat at 2-weeks old, supporting the importance to evaluate sex differences even at an age when reproductive hormones are not yet activated. 

Key Publications

Rudolph MC, Young BE, Lemas DJ, Palmer CE, Hernandez TL, Barbour LA, Friedman JE, Krebs NF, MacLean PS. Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI. Int J Obes (Lond). 2017 Apr;41(4):510-517. doi:10.1038/ijo.2016.211. Epub 2016 Nov 23. PubMed PMID: 27876761; PubMed Central PMCID: PMC5380514.

Rudolph MC, Jackman MR, Presby DM, Houck JA, WEbb PG, Johnson GC, Soderborg TK, de la Houssaye BA, Yang IV, Friedman JE, MacLean PR. Low Neonatal Plasma n-6/n-3 PUFA Ratios Regulate Offspring Adipogenic Potential and Condition Adult Obesity Resistance. Diabetes. 2018 Apr;67(4):651-661. doi:10.2337/db17-0890. Epub 2017 Nov 14. PubMed PMID: 29138256; PubMed Central PMCID: PMC5860857.

Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nat Commun. 2018 Sep 4;9(1):3592. doi: 10.1038/s41467-018-05911-0. PubMed PMID: 30181538; PubMed Central PMCID: PMC6123393.