Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells

Kim, Dae Whan; Kim, Beom Sue; Kwon, Hee Seok; Kim, Chan Gil; Lee, Han Woong; Choi, Woong; Kim, Chul Geun

doi:10.1038/emm.2003.67

Cited by 7 publications

(3 citation statements)

References 31 publications

(33 reference statements)

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“…The rise in leptin during the first week of neonatal life occurs in parallel with an increase in cell volume (72) but no change in adipocyte number (17), a loss of UCP1 and BAT (11), and the increased deposition of white adipose tissue, both around the central body organs and subcutaneously (11). The cellular mechanisms by which leptin promotes UCP2 mRNA abundance, but loss of UCP1 protein in neonatal BAT, remains to be elucidated but might involve apoptosis, which has been linked to the transformation of brown to white adipocytes in the adult mouse (35).…”

Section: Leptin and Ucp2 In Neonatal Batmentioning

confidence: 99%

Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development

Gnanalingham¹,

Mostyn²,

Webb³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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In the neonate, adipose tissue and the lung both undergo a rapid transition after birth, which results in dramatic changes in uncoupling protein abundance and glucocorticoid action. Leptin potentially mediates some of these adaptations and is known to promote the loss of uncoupling protein (UCP)1, but its effects on other mitochondrial proteins or glucocorticoid action are not known. We therefore determined the effects of acute and chronic administration of ovine recombinant leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute study, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100 μg of leptin or vehicle before tissue sampling 4 h from the start of the study, whereas in the chronic study, nine pairs of 1-day-old lambs received 100 μg of leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor, and 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 mRNA and increased 11β-HSD type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2 mRNA abundance was positively correlated to plasma leptin and nonesterified fatty acids and negatively correlated to mean colonic temperature in the leptin group at 7 days. In conclusion, leptin administration to the neonatal lambs causes differential effects on UCP2 abundance in BAT and lung. These effects may be important in the development of these tissues, thereby optimizing lung function and fat growth.

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Section: Leptin and Ucp2 In Neonatal Batmentioning

confidence: 99%

Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development

Gnanalingham¹,

Mostyn²,

Webb³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…Prior work suggested Bscl2 may play a role in brown adipose tissue function ( 83 ), however BAT-specific Bscl2 deletion showed Bscl2 is not required for brown adipogenesis, but rather plays a cell-autonomous role in mediating BAT development and function ( 84 , 85 ). Marrow adipocytes in our global Bscl2 KO and WT sections were unilocular and similar between KO and WT, though locularity and mRNA analyses ( Figure 6 ) are insufficient to exclude brown/beige properties and require additional investigations (UCP1 staining, or ultrastructural as well as bioenergetic analyses of mitochondria ( 86 , 87 ), are important for future studies. No difference in bone mRNA for sclerostin and osteocalcin was found between groups, even with exercise-induced bone formation, in line with prior work ( 14 ).…”

Section: Discussionmentioning

confidence: 91%

Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity

et al. 2022

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Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p<0.001) but not in KO. Notably, exercise increased trabecular BV/TV in both (+31%, KO-E vs KO, p=0.004; +14%, WT-E vs WT, p=0.006). The presence and distribution of BMAT in SEIPIN KO, though lower than WT, is unexpected and points to a uniqueness of this depot. That trabecular bone increases were achievable in both KO and WT, despite a difference in BMAT quantity/distribution, points to potential metabolic flexibility during exercise-induced skeletal anabolism.

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“…While it has been established that brown adipocytes produce and secrete less leptin than white adipocytes, the finding that BAT and PAT have comparable levels of leptin is further indication that PAT may resemble a beige depot as baseline [ 41 , 42 ]. Leptin mRNA levels are generally correlated with leptin secretion; both are related to adipocyte size and lipid droplet morphology and are under reciprocal regulatory control with that of UCP1 mRNA levels [ 43 , 44 ]. While higher leptin expression is associated with unilocularity and increased adipocyte size, lower leptin expression is associated with reduced adipocyte size and multilocularity which are hallmarks of brown adipocyte morphology [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Unique Genetic and Histological Signatures of Mouse Pericardial Adipose Tissue

et al. 2020

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Obesity is a major risk factor for a plethora of metabolic disturbances including diabetes and cardiovascular disease. Accumulating evidence is showing that there is an adipose tissue depot-dependent relationship with obesity-induced metabolic dysfunction. While some adipose depots, such as subcutaneous fat, are generally metabolically innocuous, others such as visceral fat, are directly deleterious. A lesser known visceral adipose depot is the pericardial adipose tissue depot. We therefore set out to examine its transcriptional and morphological signature under chow and high-fat fed conditions, in comparison with other adipose depots, using a mouse model. Our results revealed that under chow conditions pericardial adipose tissue has uncoupling-protein 1 gene expression levels which are significantly higher than classical subcutaneous and visceral adipose depots. We also observed that under high-fat diet conditions, the pericardial adipose depot exhibits greatly upregulated transcript levels of inflammatory cytokines. Our results collectively indicate, for the first time, that the pericardial adipose tissue possesses a unique transcriptional and histological signature which has features of both a beige (brown fat-like) but also pro-inflammatory depot, such as visceral fat. This unique profile may be involved in metabolic dysfunction associated with obesity.

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Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells

Cited by 7 publications

References 31 publications

Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development

Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development

Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity

Unique Genetic and Histological Signatures of Mouse Pericardial Adipose Tissue

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