Brown adipose tissue activity controls triglyceride clearance
Abstract
Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.
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Catecholamines also induce WAT lipolysis to promote the release of fatty acids, which are used as the principal substrate for BAT thermogenesis.
“Importantly, catecholamines also induce WAT lipolysis to promote the release of fatty acids, which are used as the principal substrate for BAT thermogenesis (Bartelt et al, 2011).”
From Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation (2020) · cites this paper as Bartelt et al, 2011
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BackgroundBrown Adipose Tissue Energy Metabolism in Humans
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Self-citationCold but not sympathomimetics activates human brown adipose tissue in vivo
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Perivascular Adipose Tissue in Vascular Function and Disease
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Mir193b–365 is essential for brown fat differentiation
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Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans
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Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance
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Cellular origins of cold‐induced brown adipocytes in adult mice
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Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice
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“CGI-58 Deletion in BAT Improves Metabolic Profile in Mice Energy-dissipating adipocytes contribute significantly to the handling of lipids and glucose in humans and mice (Bartelt et al., 2011; Cohen et al., 2014; Orava et al., 2011; Ouellet et al., 2012; Stanford et al., 2013).”
InfluentialFatty acid transport proteins, implications in physiology and disease
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“Cold exposure improves dyslipidemia and insulin resistance by accelerating plasma lipid clearance by triglyceride uptake into BAT in mice [124].”
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Adipocyte lineages: Tracing back the origins of fat
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Brown and beige fat: Molecular parts of a thermogenic machine
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Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans
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Endothelial cell CD36 optimizes tissue fatty acid uptake
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“(30) have shown that both LpL and CD36 affect BAT uptake of FAs during cold exposure.”
Brown Adipose Tissue Responds to Cold and Adrenergic Stimulation by Induction of FGF21
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Self-citationThyroid Hormones and the Metabolic Syndrome
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Neuronal control of peripheral insulin sensitivity and glucose metabolism
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Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders
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“Several studies have also shown that BAT activity improves glucose homeostasis and clears about 75% of the total glucose from the circulation in rodents [7,8].”
BackgroundA diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use
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“, 2012) and hepatic TG in the form of TG-rich lipoproteins (TRLs) that are known to contribute greatly to BAT lipid content during thermogenesis (Bartelt et al., 2011).”
BackgroundBrown Adipose Tissue: an Update on Recent Findings
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Brown adipose tissue and thermogenesis
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IL-37 protects against obesity-induced inflammation and insulin resistance
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Human Brown Adipose Tissue: What We Have Learned So Far
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Emerging Complexities in Adipocyte Origins and Identity
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Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation
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“The differences in glucose tolerance were greatest at later time points after glucose injection (Figure 3E) suggesting the defect in 5-BKO mice was due to decreased glucose uptake in BAT, as BAT is known to be a major site of glucose utilization in the mouse (Bartelt et al., 2011; Nedergaard et al., 2011).”
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism
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“The energy uptake of active BAT is high and results in a substantial effect on triglyceride clearance (52).”
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“This highlights an interesting paradox; in active BAT, which is best known for its catabolically high FA oxidation (Bartelt et al., 2011; Cannon and Nedergaard, 2004; Labbe et al., 2015, 2016), anabolic de novo FA synthesis pathways, which often antagonize FA oxidation (Hue and Taegtmeyer, 2009)…”
Influential
- Authors
- Bartelt, A., Bruns, O. T., Reimer, R., Hohenberg, H., Ittrich, H., Peldschus, K., Kaul, M. G., Tromsdorf, U. I., Weller, H., Waurisch, C., Eychmüller, A., Gordts, P. L. S. M., Rinninger, F., Bruegelmann, K., Freund, B., Nielsen, P., Merkel, M., & Heeren, J.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Universität Hamburg (DE)
- Technische Universität Dresden (DE)
- KU Leuven (BE)
- Corresponding author
- Bartelt, Alexander
- ORCID
- Venue
- Nature Medicine
- Published
- 2011-01-23
- Volume
- 17
- Issue
- 2
- Pages
- 200-205
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2162023168
- Cited by
- 1,608
- References
- 37
- Citations by year
- 2026: 49 · 2025: 75 · 2024: 82 · 2023: 110 · 2022: 115 · 2021: 133 · 2020: 134 · 2019: 141 · 2018: 130 · 2017: 129 · 2016: 112 · 2015: 128 · 2014: 88 · 2013: 87 · 2012: 66
- FWCI
- 58.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- brown adipose tissue, triglyceride clearance, triglyceride-rich lipoproteins, lipoprotein lipase, CD36, cold exposure, hyperlipidemia, insulin resistance, obesity, cardiovascular disease, lipoprotein metabolism, remnant lipoproteins
- MeSH terms
- Animals, Body Temperature Regulation, Adipose Tissue, Brown, Cholesterol, Cold Temperature, Humans, Hyperlipidemias, Insulin Resistance, Lipoprotein Lipase, Lipoproteins, Male, Mice, Inbred C57BL, Obesity, Triglycerides, CD36 Antigens, Vascular Endothelial Growth Factor A, Mice
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