Mount Sinai Researchers Uncover How Mammary Glands Control Overall Energy Balance and Fat Metabolism
An Icahn School of Medicine at Mount Sinai study sheds light on the intricate interplay between mammary adipose (fat) tissue and breast health, and offers exciting possibilities for understanding breast development, lactation, cancer, and obesity and related metabolic disorders.
The study was published today in Nature. The research team was led by Prashant Rajbhandari, PhD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease), and a member of the Diabetes, Obesity, and Metabolism Institute at Icahn Mount Sinai.
The researchers discovered a new family of locally secreted and locally acting molecules in the breast called “mammokines” that contribute not only to normal mammary biology, but to overall fat cell physiology and energy balance control.
Mammary adipose tissue has long been recognized for its essential role in breast biology. It consists of many different cell types, including fat cells (adipocytes), immune cells, sympathetic nerve fibers, and mammary epithelial cells forming a milk-producing ductal system. Mammary adipocytes play important roles in organizing mammary ducts, and the reverse is true as well.
The new studies reveal an unexpected role for nerve-activated ductal cells in mammary adipocyte metabolism and heat generation. These mammary duct-secreted mammokines play an important role in controlling mammary gland fat abundance and could potentially orchestrate critical processes involved in breast development, lactation, and overall whole-body metabolic regulation. The findings thus have important implications for breast cancer, lactation-related disorders, newborn health, and metabolic syndromes linked to mammary adipose dysfunction.
“The discovery of mammokines is a significant milestone in our quest to comprehend the complex interplay between mammary adipose tissue and breast biology,” says Dr. Rajbhandari “This breakthrough opens up new avenues for developing targeted interventions to improve breast health and combat related metabolic disorders.”
The research team is currently focused on working to further identify new mammokines and characterize each of them. Their primary aim is to decipher the precise roles of these mammokines and determine whether they regulate systemic glucose and insulin homeostasis through communication with the brain, liver, and pancreas. Additionally, the team is exploring potential therapeutic applications for diseases related to the breast and metabolism.
“This work holds enormous promise for future advancements in women's health and metabolic research and the development of personalized treatment strategies based on mammokine profiling,” said Andrew Stewart, MD, Director of the Diabetes, Obesity, and Metabolism Institute at Icahn Mount Sinai.
This discovery is the result of the collaborative efforts of a large team of researchers with diverse areas of expertise in the United States and Europe. Research contributors include Sanil Patel, MS; Njeri Z.R. Sparman, BS; Alexandra Alvarsson, PhD; Luís C. Santos, PhD; Samuel J. Duesman, PhD; Chung Hwan Cho, PhD; Ephraim Hathaway, BS; Abha K. Rajbhandari, PhD; Peng Wang, PhD; Leigh Goedeke, PhD; Sarah A. Stanley, PhD, and Prashant Rajbhandari, PhD, Icahn Mount Sinai, along with Douglas Arneson, PhD; In Sook Ahn, PhD; Graciel Diamante, PhD; Ingrid Cely, BS; Xia Yang, PhD, and Aldons J. Lusis, PhD, University of California, Los Angeles; Alessia Centonze, PhD, and Cédric Blanpain, PhD, Université Libre de Bruxelles; Noble Kumar Talari, PhD, and Karthickeyan Chella Krishnan, PhD, University of Cincinnati College of Medicine, plus Atul J. Butte, PhD, University of California, San Francisco.
Dr. Rajbhandari is supported by The Icahn School of Medicine at Mount Sinai Seed Fund, DK114571, NIDDK-supported Einstein-Sinai Diabetes Research Center (DRC) Pilot & Feasibility Award, and Diabetes Action Research and Education Foundation (DREF) Grant #501. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.
Ranked 14th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 44 academic departments and 36 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases.
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About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties.