how mammary glands control overall energy balance and fat metabolism

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 studiesreveal 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.

Icahn Mount Sinai offers highly competitive MD, PhD, and Master's degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System.

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai's technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public.

Icahn Mount Sinai's commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School's programs.

Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai's location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.