Cidea improves the metabolic profile through expansion of adipose tissue

Abreu-Vieira, Gustavo; Fischer, Alexander W.; Mattsson, Charlotte L.; Jong, Jasper de; Shabalina, Irina G.; Rydén, Mikael; Laurencikiene, Jurga; Cannon, Barbara; Nedergaard, Jan; Petrovič, Nataša

doi:10.1038/ncomms8433

Cited by 86 publications

(88 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cold stress increases catecholamine levels, thereby activating nonshivering thermogenesis in BAT and substantially increasing food intake and metabolic rate [22]. Thus, it has been informative to characterize mouse models with genetic alterations in energy storage at room temperature (23 °C) versus thermoneutrality (30 °C), a temperature that poses no thermal stress and little BAT activation [23], [34], [35]. Recently, it has been demonstrated that housing mice with LD protein deficiencies at thermoneutrality reveals phenotypes that more closely resemble lipodystrophic syndromes in humans with mutations in LD protein genes [36].…”

Section: Resultsmentioning

confidence: 99%

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

DiStefano

Flach

Senol-Cosar

et al. 2016

Molecular Metabolism

View full text Add to dashboard Cite

ObjectiveAdipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis.MethodWhite and brown adipocyte-deficient (Hig2fl/fl × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process.ResultsHig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl × Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes.ConclusionsWe conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 °C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

DiStefano

Flach

Senol-Cosar

et al. 2016

Molecular Metabolism

View full text Add to dashboard Cite

show abstract

“…On the one hand, overexpression of glucose transporter GLUT4 (Shepherd et al, 1993) or mitochondrial protein mitoNEET (Kusminski et al, 2012) in WAT, with the consequent increase in fat mass, has been shown to enhance insulin sensitivity. In turn, increased adipose tissue expandability also resulted in an improved metabolic profile under a high-fat diet (Abreu-Vieira et al, 2015). On the other hand, blockage of adipose tissue expandability is associated with severe metabolic alterations (Medina-Gomez et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Sexual Dimorphism in the Age-Induced Insulin Resistance, Liver Steatosis, and Adipose Tissue Function in Rats

et al. 2017

View full text Add to dashboard Cite

Age-linked metabolic disturbances, such as liver steatosis and insulin resistance, show greater prevalence in men than in women. Thus, our aim was to analyze these sex-related differences in male and female Wistar rats (aged 26 days and 3, 7, and 14 months), and to assess their potential relationship with alterations in the capacity of adipose tissue expansion and the dysregulation of the main adipokines produced by the adipose tissue, leptin and adiponectin. Adiposity-related parameters, blood parameters, the expression of genes related to expandability and inflammation (WAT), lipid metabolism (liver), and leptin and insulin signaling (both tissues) were measured. In females, adiposity index and WAT DNA content gradually increased with age, whereas males peaked at 7 months. A similar sex-dependent pattern was observed for leptin expression in WAT, while Mest expression levels decreased with age in males but not in females. Females also showed increased expression of the proliferation marker PCNA in the inguinal WAT compared to males. In males, leptin/adiponectin ratio greatly increased from 7 to 14 months in a more acute manner than in females, along with an increase in HOMA-IR index and hepatic triacylglyceride content, while no changes were observed in females. In liver, 14-month-old males displayed decreased mRNA levels of Insr, Ampkα2, and Cpt1a compared with levels at 7 months. Males also showed decreased mRNA levels of Obrb (both tissues), and increased expression levels of Cd68 and Emr1 (WAT) with age. In conclusion, females are more protected from age-related metabolic disturbances, such as insulin resistance, hepatic lipid deposition, and WAT inflammation compared to males. This may be related to their greater capacity for WAT expansion—reflected by a greater Mest/leptin mRNA ratio—and to their ability to maintain adiponectin levels and preserve leptin sensitivity with aging.

show abstract

“…and were transferred to metabolic chambers as previously described [54]. The mice were measured at 33 °C to obtain basal values during 10 min.…”

Section: Methodsmentioning

confidence: 99%

β 3 -Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: Mediation through the mTOR pathway

Olsen

Csikasz

Dehvari

et al. 2017

Molecular Metabolism

Self Cite

View full text Add to dashboard Cite

ObjectiveToday, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for in vivo quantification of BAT activity in adult humans. The underlying assumption is that the glucose uptake reflects the thermogenic activity of the tissue.MethodsTo examine this basic assumption, we here followed [18F]FDG uptake by PET and by tissue [3H]-2-deoxy-d-glucose uptake in wildtype and UCP1(−/−) mice, i.e. in mice that do or do not possess the unique thermogenic and calorie-consuming ability of BAT.ResultsUnexpectedly, we found that β3-adrenergically induced (by CL-316,243) glucose uptake was UCP1-independent. Thus, whereas PET-FDG scans adequately reflect glucose uptake, this acute glucose uptake is not secondary to thermogenesis but is governed by an independent cellular signalling, here demonstrated to be mediated via the previously described KU-0063794-sensitive mTOR pathway.ConclusionsThus, PET-FDG scans do not exclusively reveal active BAT deposits but rather any tissue possessing an adrenergically-mediated glucose uptake pathway. In contrast, we found that the marked glucose uptake-ameliorating effect of prolonged β3-adrenergic treatment was UCP1 dependent. Thus, therapeutically, UCP1 activity is required for any anti-diabetic effect of BAT activation.

show abstract

Cidea improves the metabolic profile through expansion of adipose tissue

Cited by 86 publications

References 58 publications

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

Sexual Dimorphism in the Age-Induced Insulin Resistance, Liver Steatosis, and Adipose Tissue Function in Rats

β 3 -Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: Mediation through the mTOR pathway

Contact Info

Product

Resources

About