Abstract
Key points
White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear. Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non-selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator-activated receptor (PPAR) coactivator-1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation. The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti-obesity therapies.Abstract
Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic-profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)-immunopositive paucilocular adipocytes containing peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) and PR domain-containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC-1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold acclimation. Compared with controls (22 ± 1 °C), levels of UCP1 mRNA increased in parallel with PPARγ (PPARα from days 1 to 7 and PGC-1α on day 1). Transcriptional recruitment of rpWAT was followed by an increase in UCP1 protein content (from days 1 to 21). Results clearly showed that most of the adipocytes within rpWAT underwent transient brown-fat-like thermogenic recruitment upon stimulation, but only a minority of cells retained a brown adipose tissue-like phenotype after the attainment of cold acclimation. Therefore, browning of WAT is dependent on both maintaining the thermogenic response and retaining enough brown-like thermogenically competent adipocytes in the long-term. Both aspects of browning could be important for long-term energy homeostasis and body-weight regulation.Full text links
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References
Articles referenced by this article (62)
Brown adipose tissue: function and physiological significance.
Physiol Rev, (1):277-359 2004
MED: 14715917
Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure.
Diabetes, (10):3253-3265 2014
MED: 24789919
FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance.
Cell, (5):563-573 2001
MED: 11551504
Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization.
J Cell Sci, 931-942 1992
MED: 1362571
Reporting ethical matters in the Journal of Physiology: standards and advice.
J Physiol, (Pt 4):713-719 2009
MED: 19218620
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis.
Genes Dev, (3):271-281 2012
MED: 22302939
Distribution and development of brown adipocytes in the murine and human adipose organ.
Cell Metab, (4):253-256 2010
MED: 20374956
Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a beta3-adrenoceptor agonist.
Biochem Pharmacol, (1):121-131 1997
MED: 9296358
Sensory nerves affect the recruitment and differentiation of rat periovarian brown adipocytes during cold acclimation.
J Cell Sci, 2587-2594 1998
MED: 9701557
Mitochondrial turnover: a phenotype distinguishing brown adipocytes from interscapular brown adipose tissue and white adipose tissue.
J Biol Chem, (13):8243-8255 2015
MED: 25645913
Show 10 more references (10 of 62)
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Funding
Funders who supported this work.
Ministry of Education, Science and Technological Development of the Republic of Serbia (1)
Grant ID: 173054, 173055