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Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans
Open accessAbstract
Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans.
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Citations
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058
High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans
Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., et al. (2009) · Diabetes · doi:10.2337/db09-0530 · Cited by 1,848
Unexpected evidence for active brown adipose tissue in adult humans
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00691.2006 · Cited by 1,824
Brown adipose tissue activity controls triglyceride clearance
Bartelt, A., Bruns, O. T., Reimer, R., Hohenberg, H., Ittrich, H., Peldschus, K., Kaul, M. G., Tromsdorf, U. I., Weller, H., Waurisch, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2297 · Cited by 1,608
Brown adipose tissue regulates glucose homeostasis and insulin sensitivity
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Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy
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“Thyroid hormones and leptin can improve insulin sensitivity (Lin et al., 2002; Lin and Sun, 2011; Petersen et al., 2002; Sivitz et al., 1997), and they have been linked with increased BAT activity (Chondronikola et al.”
BackgroundSensory and sympathetic nervous system control of white adipose tissue lipolysis
Bartness, T. J., Shrestha, Y. B., Vaughan, C. H., Schwartz, G. J., & Song, C. K. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.031 · Cited by 289 · cited 2×
“During periods of negative energy balance (e.g., cold-induced BAT activation), increased sympathetic tone promotes lipolysis, thereby increasing FFA availability (Bartness et al., 2010).”
BackgroundCentral leptin increases insulin sensitivity in streptozotocin-induced diabetic rats
Lin, C.-Y., Higginbotham, D. A., Judd, R. L., & White, B. D. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00489.2001 · Cited by 124
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Brown adipose tissue is associated with cardiometabolic health
Becher, T., Palanisamy, S., Kramer, D. J., Eljalby, M., Marx, S. J., Wibmer, A. G., Butler, S. D., Jiang, C. S., Vaughan, R., Schöder, H., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-1126-7 · Cited by 743
GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice
Samms, R. J., Christe, M. E., Collins, K. A. L., Pirro, V., Droz, B. A., Holland, A. K., Friedrich, J. L., Wojnicki, S., Konkol, D. L., Cosgrove, R., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146353 · Cited by 256
Adipose Tissue and Metabolic Health
An, S.-M., Cho, S.-H., & Yoon, J. C. (2023) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0011 · Cited by 184
A causal role for hyperinsulinemia in obesity
Templeman, N. M., Skovsø, S., Page, M. M., Lim, G. E., & Johnson, J. D. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0449 · Cited by 168
Human and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function
Porter, C., Herndon, D. N., Chondronikola, M., Chao, T., Annamalai, P., Bhattarai, N., Saraf, M. K., Capek, K. D., Reidy, P. T., Daquinag, A. C., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.004 · Cited by 148
Self-citationMitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge
Lu, Y., Fujioka, H., Joshi, D., Li, Q., Sangwung, P., Hsieh, P., Zhu, J., Torio, J., Sweet, D., Wang, L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26394-5 · Cited by 76
Jiang, N., Yang, M., Han, Y., Zhao, H., & Sun, L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.870250 · Cited by 68
Roy, D., & Tedeschi, A. (2021) · Cells · doi:10.3390/cells10051078 · Cited by 68
Michael, N. J., Simonds, S. E., van den Top, M., Cowley, M. A., & Spanswick, D. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.002 · Cited by 21
Targeting skeletal muscle mitochondrial health in obesity
Pileggi, C. A., Hooks, B. G., McPherson, R., Dent, R. R. M., & Harper, M.-E. (2022) · Clinical Science · doi:10.1042/cs20210506 · Cited by 21
Metadata
- Authors
- Chondronikola, M., Volpi, E., Børsheim, E., Porter, C., Saraf, M. K., Annamalai, P., Yfanti, C., Chao, T., Wong, D., Shinoda, K., Labbė, S. M., Hurren, N. M., Cesani, F., Kajimura, S., & Sidossis, L. S.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 1200-1206
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2403047053
- Cited by
- 326
- References
- 10
- FWCI
- 25.78
- Type
- journal article
- Language
- en
- Open access
- bronze
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