Adilson Guilherme, PhD
Associate Professor, Program in Molecular Medicine
Postdoctoral Studies, University of Massachusetts Chan Medical School, laboratory of Michael Czech, PhD
PhD, Biochemistry, Federal University of Rio de Janeiro (Brazil)
Adipocyte Metabolism & Insulin Signaling
The Guilherme lab investigates molecular and cellular mechanisms by which adipocytes regulate systemic glucose and lipid metabolism. Our research focuses on how these mechanisms are disrupted in obesity, leading to systemic insulin resistance and the development of type 2 diabetes.
Using advanced genetic models, CRISPR-engineered adipocytes, and metabolic flux analysis, we explore how nutrient sensing, transcriptional regulation, and nuclear-to-lipid droplet inter-organelle communication shape adipocyte function in health and metabolic disease.
Guilherme Lab Research Themes
- Mechanisms of Insulin Resistance in Adipose Tissue
- Metabolic Flux Alterations in Obese Adipocytes Promoting Insulin Resistance
- Lipid Droplet - Nuclear Crosstalk in Adipocyte Metabolism
- Adipocyte De Novo Lipogenesis as a Regulator of Systemic Metabolism
Dr. Guilherme's research has evolved from dissecting molecular mechanisms of signaling and membrane trafficking in adipocytes to uncovering how adipocyte pathways regulate systemic metabolic homeostasis and how these processes are disrupted in obesity and related metabolic disorders. He has led multiple research projects resulting in impactful discoveries published in high-profile journals.
Notable Achievements
Discovery of a key downstream target of insulin-stimulated PIP3 generation
We developed a novel method to use lipids as ligands/baits to identify proteins interacting with PIP3 (Science, 275, 1927–1930).
Identification of GLUT4-membrane proteins essential for insulin-regulated glucose transport
Using proteomics, we uncovered new regulators of GLUT4 trafficking (Nature, 420, 19–26).
Development of siRNA screening methods to identify regulators of adipocyte metabolism
We pioneered siRNA-based approaches to discover genes controlling insulin action on glucose transport in adipocytes (PNAS, 103, 2087–2092).
Current Projects
Recently, Dr. Guilherme has focused his research on addressing fundamental questions related to:
- The crosstalk between adipose tissue and other organs in regulating energy balance and systemic metabolism
- Strategies to improve adipose tissue health in the context of obesity and obesity-associated metabolic dysfunction.
To investigate these topics, he has developed innovative tools that enable precise interrogation of key metabolic pathways within adipocytes, particularly de novo lipogenesis (DNL) and its lipid-derived metabolites, and their roles in regulating adipocyte function and whole-body insulin sensitivity.
de novo synthesis of palmitate in white adipocytes suppresses thermogenesis
As part of this effort, Dr. Guilherme and his team generated a comprehensive panel of adipose-specific single and double knockout mouse models to interrogate the roles of DNL enzymes in adipocyte function and systemic metabolic homeostasis. Focusing on key DNL enzymes—including ACLY, ACC1, ACC2, MCD, and FASN—they demonstrated that loss of palmitate production, rather than the accumulation of upstream intermediates such as acetyl-CoA or malonyl-CoA, is necessary and sufficient to induce browning of white adipose tissue. These findings reveal a novel mechanism by which lipid metabolic flux within adipocytes regulates adipose remodeling and systemic insulin sensitivity. This work was recently published in Cell Reports (PMID: 37163372).
Review Articles
Dr. Guilherme authored several highly cited and influential review articles that have shaped current understanding of adipocyte signaling, sympathetic innervation, and the endocrine regulation of metabolism in both healthy and diseased states:
The Adipocyte Supersystem of Insulin and cAMP Signaling. Guilherme A., Rowland L.A., Wang H., Czech M.P. (2023). Trends in Cell Biology, 33(5): 340–354. [PMID: 35989245]
This review presents a unified framework describing how insulin and cAMP signaling pathways intersect in adipocytes to regulate energy metabolism.
Molecular Pathways Linking Adipose Innervation to Insulin Action in Obesity and Diabetes Mellitus. Guilherme A., Henriques F., Bedard A.H., Czech M.P. (2019). Nature Reviews Endocrinology, 15(4): 207–225. [PMID: 30733616]
This work highlights the emerging role of adipose tissue innervation in regulating insulin sensitivity and energy homeostasis.
Adipocyte Dysfunctions Linking Obesity to Insulin Resistance and Type 2 Diabetes. Guilherme A., Virbasius J.V., Puri V., Czech M.P. (2008). Nature Reviews Molecular Cell Biology, 9(5): 367–377. [PMID: 18401346]
A foundational review elucidating how cellular defects in adipocytes contribute to systemic metabolic dysfunction in obesity.
Recent Publications
Acetyl-CoA Carboxylase 1 is a Suppressor of the Adipocyte Thermogenic Program. Guilherme A., Rowland L.A., Wetoska N., Tsagkaraki E., Santos K.B., Bedard A.H., Henriques F., Kelly M., Munroe S., Pedersen D.J., Ilkayeva O.R., Koves T.R., Tauer L., Pan M., Han X., Kim J.K., Newgard C.B., Muoio D.M., Czech M.P. (2023). Cell Reports, 42(5):112488. [PMID: 37163372]
This study demonstrates that Acetyl-CoA Carboxylase 1 (ACC1) plays a critical role in suppressing the thermogenic program in adipocytes, providing new insights into adipocyte metabolism and thermogenesis.
De Novo Lipogenesis Fuels Adipocyte Autophagosome and Lysosome Membrane Dynamics. Rowland L.A., Guilherme A., Henriques F., DiMarzio C., Munroe S., Wetoska N., Kelly M., Reddig K., Hendricks G., Pan M., Han X., Ilkayeva O.R., Newgard C.B., Czech M.P. (2023). Nature Communications, 14(1):1362. [PMID: 36914626]
This work explores how de novo lipogenesis in adipocytes supports membrane dynamics of autophagosomes and lysosomes, revealing a new link between lipid metabolism and cellular degradation pathways.
Control of Adipocyte Thermogenesis and Lipogenesis Through β3-Adrenergic and Thyroid Hormone Signal Integration. Guilherme A., Yenilmez B., Bedard A.H., Henriques F., Liu D., Lee A., Goldstein L., Kelly M., Nicoloro S.M., Chen M., Weinstein L., Collins S., Czech M.P. (2020). Cell Reports, 31(5):107598. [PMID: 32375048]
This study uncovers how β3-adrenergic and thyroid hormone signaling integrate to regulate both thermogenesis and lipogenesis in adipocytes, providing insights into how hormonal crosstalk shapes adipose tissue function.
Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis. Henriques F., Bedard A.H., Guilherme A., Kelly M., Chi J., Zhang P., Lifshitz L.M., Bellvé K., Rowland L.A., Yenilmez B., Kumar S., Wang Y., Luban J., Weinstein L.S., Lin J.D., Cohen P., Czech M.P. (2020). Cell Reports, 32(5):107998. [PMID: 32755590]
This publication uses single-cell RNA profiling to identify adipocyte-to-macrophage signaling pathways that promote thermogenesis, offering a novel perspective on intercellular communication in thermogenic regulation.