Adipocytes, also referred to simply as fat cells, are too frequently misconceived as passive repositories for stored calories. In reality, adipocytes do much more than store fat. These metabolically active cells play central roles in energy balance, thermogenesis, inflammation, and general metabolic regulation. Even the term adipocyte derives from the Latin words adipo (fat) and cyte (cell), which underscores their basic function in the body’s intricate physiological mechanisms. Their influence on metabolic homeostasis is both significant and complex.
A Posse of Cell Types
The adipocyte domain is multifaceted, comprising white, brown, and beige types. White adipocytes are energy storage depots of subcutaneous and visceral fat, while brown adipocytes, packed with mitochondria and containing uncoupling protein 1 (UCP-1), generate heat through non-shivering thermogenesis [1]. Beige adipocytes, which occur in white fat stores in response to specific stimuli like cold, combine the features of both white and brown adipocytes, making the body more metabolically flexible [2]. The research postulates that white adipocytes’ ability to switch to beige cells is crucial in controlling obesity and other metabolic disease states [3].
Turning Fat into Heat
Thermogenesis, or the production of heat, is primarily controlled by brown and beige adipocytes [4–5]. When activated, these cells use energy and burn calories, thus maintaining body temperature. The molecular controllers of this process, such as PGC-1α and PRDM16, have been extensively researched for their capacity to induce UCP1 expression and mitochondrial activity [6–7]. Recent studies are investigating how to trigger white adipocytes to be transformed into beige adipocytes, which can be of therapeutic use against obesity [6–7].
Dysfunctional Engines
Not all fat cells contribute to metabolism. Growth of white adipose tissue, especially visceral fat, results in chronic inflammation and metabolic illness. This type of inflammation is triggered by immune cell activation and cytokines, which results in insulin resistance in organs and the development of type 2 diabetes [8–10]. Experiments have shown that nuclear receptors like PPARγ suppress inflammation in fat tissue and thereby present new options for potential therapies [11–12].
The Small Cells with Great Impact
Adipocytes are not fixed. Their ability to adapt, either by altering their function or altering their type, is invaluable in order to maintain the body in balance. For example, during cold, white adipocytes have the ability to transform into beige fat cells, which are thermogenic. This adaptability is important in managing energy levels and coping with metabolic demands. Our greater insight into the signal pathways that govern adipocyte plasticity has opened up new avenues for intervention in obesity and related diseases [13–15].
New Fat Cells are Generated and Old Ones are Replaced
Modern science has refuted the long-standing belief that fat cells are inert, and rather, it has been discovered that adipocyte turnover is an ongoing process [16–17]. Diet, exercise, and metabolic well-being all profoundly influence the rate of replacement of fat cells. Turnover rates also vary with the type of fat, with visceral fat being replaced faster than subcutaneous fat [18]. All of this contradicts conventional knowledge regarding fat cell biology and gives a new direction to improve metabolic well-being [19].
The Metabolic Storm
Adipocytes play a pivotal role in the pathogenesis of a variety of metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease [14–15, 20]. Visceral versus subcutaneous fat’s biphasic effects on overall well-being emphasize adipose tissue’s complex nature. By illuminating inter-relationships between adipocyte activity and systemic metabolism, scientists are striving to give targeted therapies to profit from the beneficial properties of brown and beige adipocytes but also to undo the damaging consequences of excess white fat [2, 5, 20–21].
With ongoing research into adipocytes, the intricate way in which fat cells maintain metabolic health is being uncovered. By tapping into the regenerative and thermogenic ability of these cells, scientists are providing the entry point for revolutionary ways to treat metabolic disease.
Recognizing and appreciating the labs working in this space
- Seale Lab: University of Pennsylvania/ Perelman School of Medicine, Philadelphia, PA, USA. https://www.med.upenn.edu/sealelab/ , X: @LabSeale
- Spiegelman Lab: Harvard Medical School & Dana Farber Cancer Institute. Boston, MA, USA. https://labs.dana-farber.org/spiegelmanlab/research , X: @LabSpiegelman
- Lazar Lab: University of Pennsylvania, Philadelphia, PA, USA. https://lazarlabpenn.com/
- Gupta Lab: UT Southwestern Medical Center, Dallas, TX, USA. https://touchstonelabs.org/r-gupta-lab
- Cohen Lab: The Rockefeller University, New York, NY, USA. https://cohenlab.rockefeller.edu/
- Spalding Lab: Karolinska Institute, Solna, Sweden. https://www.spaldinglab.org/ , X: @SpaldingLab
- O’Rourke Lab: University of Michigan Medical School, Ann Arbor, MI, USA. https://medresearch.umich.edu/labs-departments/research-labs/orourke-lab/
- Ferrante Lab: Columbia University, New York, NY, USA. https://www.ferrantelab.org/
- Rodeheffer Lab: Yale School of Medicine, New Haven, CT, USA. https://medicine.yale.edu/lab/rodeheffer/
- Deplancke Lab: École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. https://www.epfl.ch/labs/deplanckelab/
References
- Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–468.
- Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab. 2010;11(4):257–262.
- Seale P, Bjork B, Yang W, Kajimura S, Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454(7207):961–967.
- Gupta RK, Arany Z, Seale P, et al. Transcriptional control of preadipocyte determination by Zfp423. Nature. 2010;464(7288):619–623.
- Gupta RK, Mepani RJ, Kleiner S, et al. Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab. 2012;15(2):230–239.
- Ahmadian M, Suh JM, Hah N, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19(5):557–566.
- Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem. 2008;77:289–312.
- Chi J, Wu Z, Choi CHJ, et al. Three-dimensional adipose tissue imaging reveals regional variation in beige fat biogenesis and PRDM16-dependent sympathetic neurite density. Cell Metab. 2018;27(1): 226–236.e3
- Cohen P, Spiegelman BM. Brown and beige fat: Brown and Beige Fat: Molecular Parts of a Thermogenic Machine. Diabetes. 2015;64(7):2346–2351.
- Spalding KL, Arner E, Westermark PO, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783–787.
- Arner P, Spalding KL. Fat cell turnover in humans. Biochem Biophys Res Commun. 2010;396(1):101–104.
- O’Rourke RW, White AE, Metcalf MD, et al. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells. Diabetologia. 2011;54(6):1480–1490.
- O’Rourke RW, Metcalf MD, White AE, et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. Int J Obes (Lond). 2009;33(9):978–990.
- Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–1808.
- Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–1830.
- Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell. 2008;135(2):240–249.
- Birsoy K, Berry R, Wang T, et al. Analysis of gene networks in white adipose tissue development reveals a role for ETS2 in adipogenesis. Development. 2011;138(21):4709–4719.
- Schwalie PC, Dong H, Zachara M, et al. A stromal cell population that inhibits adipogenesis in mammalian fat depots. Nature. 2018;559(7712):103–108.
- Gubelmann C, Schwalie PC, Raghav SK, et al. Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network. Elife. 2014;3:e03346.
- Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell. 2001;104(4):531–543.
- Cohen P, Kajimura S. The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol. 2021;22(6):393–409.
About the author:
DR. CHRISTY KESTNER
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Christy Kestner holds a PhD in Neuroimmunology from the Medical University of South Carolina (MUSC), where she studied how complement drives pathological conditions related to neuroinflammation and brain injury (stroke and traumatic brain injury), as well as approaches to reduce harmful complement activation. She later conducted postdoctoral research in oncology therapeutic development, investigating new drug targets for pancreatic cancer. Dr. Kestner currently works as a scientific and medical writer, creating educational content and op-eds for science and health communication platforms. She also runs her own science communication platform, Brain & Beyond, aimed at translating complex research into accessible content. Passionate about science storytelling, she is dedicated to making immunology and neuroscience both accurate and engaging for diverse audiences.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
