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Browsing by Subject "Brown adipose tissue"
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Item Chewing the Fat: A Metabolic Role for Ldb1 Beyond the Pancreas?(Endocrine Society, 2017-04-29) Sims, Emily K.; Pediatrics, School of MedicineItem Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation(Cell Press, 2019-11-05) Mayeuf-Louchart, Alicia; Lancel, Steve; Sebti, Yasmine; Pourcet, Benoit; Loyens, Anne; Delhaye, Stéphane; Duhem, Christian; Beauchamp, Justine; Ferri, Lise; Thorel, Quentin; Boulinguiez, Alexis; Zecchin, Mathilde; Dubois-Chevalier, Julie; Eeckhoute, Jérôme; Vaughn, Logan T.; Roach, Peter J.; Dani, Christian; Pederson, Bartholomew A.; Vincent, Stéphane D.; Staels, Bart; Duez, Hélène; Biochemistry and Molecular Biology, School of MedicineBrowning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs.Item Hypothalamic Neural Circuits Regulating Energy Expenditure(Elsevier, 2025) Basu, Rashmita; Flak, Jonathan N.; Pharmacology and Toxicology, School of MedicineThe hypothalamus plays a central role in regulating energy expenditure and maintaining energy homeostasis, crucial for an organism's survival. Located in the ventral diencephalon, it is a dynamic and adaptable brain region capable of rapid responses to environmental changes, exhibiting high anatomical and cellular plasticity and integrates a myriad of sensory information, internal physiological cues, and humoral factors to accurately interpret the nutritional state and adjust food intake, thermogenesis, and energy homeostasis. Key hypothalamic nuclei contain distinct neuron populations that respond to hormonal, nutrient, and neural inputs and communicate extensively with peripheral organs like the gastrointestinal tract, liver, pancreas, and adipose tissues to regulate energy production, storage, mobilization, and utilization. The hypothalamus has evolved to enhance energy storage for survival in famine and scarce environments but contribute to obesity in modern contexts of caloric abundance. It acts as a master regulator of whole-body energy homeostasis, rapidly adapting to ensure energy supplies for cellular functions. Understanding hypothalamic function, pertaining to energy expenditure, is crucial for developing targeted interventions to address metabolic disorders, offering new insights into the neural control of metabolic states and potential therapeutic strategies.Item Tissue oxidative metabolism can increase the difference between local temperature and arterial blood temperature by up to 1.3oC: Implications for brain, brown adipose tissue, and muscle physiology(Taylor & Francis, 2018-04-04) Zaretsky, Dmitry V.; Romanovsky, Andrej A.; Zaretskaia, Maria V.; Molkov, Yaroslav I.; Emergency Medicine, School of MedicineTissue temperature increases, when oxidative metabolism is boosted. The source of nutrients and oxygen for this metabolism is the blood. The blood also cools down the tissue, and this is the only cooling mechanism, when direct dissipation of heat from the tissue to the environment is insignificant, e.g., in the brain. While this concept is relatively simple, it has not been described quantitatively. The purpose of the present work was to answer two questions: 1) to what extent can oxidative metabolism make the organ tissue warmer than the body core, and, 2) how quickly are changes in the local metabolism reflected in the temperature of the tissue? Our theoretical analysis demonstrates that, at equilibrium, given that heat exchange with the organ is provided by the blood, the temperature difference between the organ tissue and the arterial blood is proportional to the arteriovenous difference in oxygen content, does not depend on the blood flow, and cannot exceed 1.3oC. Unlike the equilibrium temperature difference, the rate of change of the local temperature, with respect to time, does depend on the blood flow. In organs with high perfusion rates, such as the brain and muscles, temperature changes occur on a time scale of a few minutes. In organs with low perfusion rates, such changes may have characteristic time constants of tens or hundreds of minutes. Our analysis explains, why arterial blood temperature is the main determinant of the temperature of tissues with limited heat exchange, such as the brain.