A large proportion of mediastinal and perirenal visceral fat of Siberian adult people is formed by UCP1 immunoreactive multilocular and paucilocular adipocytes

Efremova, A.V.; Senzacqua, Martina; Venema, Wiebe; Isakov, Evgeny; Vincenzo, Angelica Di; Zingaretti, Maria Cristina; Protasoni, Marina; Thomski, Mikhail; Giordano, Antonio; Cinti, Saverio

doi:10.1007/s13105-019-00721-4

Cited by 42 publications

(34 citation statements)

References 39 publications

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“…Human PRAT has been shown to possess unilocular and multilocular UCP1 + adipocytes (462,463). Indeed, several studies associated PRAT browning with aging and the female sex (464,465).…”

Section: Perirenal Adipose Tissuementioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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“…Human PRAT has been shown to possess unilocular and multilocular UCP1 + adipocytes (462,463). Indeed, several studies associated PRAT browning with aging and the female sex (464,465).…”

Section: Perirenal Adipose Tissuementioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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“…We recently demonstrated that cold-exposed Siberian adults (living outdoor) display higher browning of visceral adipose depots compared to individuals living in thermoneutral conditions [20]. The aim of this study was to explore whether Siberian subjects belonging to the same population also exhibit a differential PBMC expression of the markers identified by Palou and colleagues.…”

Section: Discussionmentioning

confidence: 92%

“…However, it is unknown whether brown/beige markers' expression in human PBMC is detectable and whether it varies depending on cold-exposure. We recently showed that cold-exposed Siberian adults (living outdoor) display greater β-adrenergic activation and browning of visceral adipose depots compared to individuals living in thermoneutral conditions [20]. The main objective of our study was to evaluate whether PBMC of cold-exposed Siberian miners expresses different levels of the brown/beige and fatty acid utilization markers compared to the PBMC of Siberian adults living in thermoneutral conditions.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of Browning in Cold Exposed Siberian Adults

Efremova¹,

Colleluori

Thomsky³

et al. 2020

Nutrients

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Cold-exposure promotes energy expenditure by inducing brown adipose tissue (BAT) thermogenesis, which over time, is also sustained by browning, the appearance, or increase, of brown-like cells into white fat depots. Identification of circulating markers reflecting BAT activity and browning is crucial to study this phenomenon and its triggers, also holding possible implications for the therapy of obesity and metabolic diseases. Using RT-qPCR, we evaluated the peripheral blood mononuclear cells (PBMC) expression profile of regulators of BAT activity (CIDEA, PRDM16), white adipocytes browning (HOXC9 and SLC27A1), and fatty acid β-oxidation (CPT1A) in 150 Siberian healthy miners living at extremely cold temperatures compared to 29 healthy subjects living in thermoneutral conditions. Anthropometric parameters, glucose, and lipid profiles were also assessed. The cold-exposed group showed significantly lower weight, BMI, hip circumference, and PBMC expression of CIDEA, but higher expression of HOXC9 and higher circulating glucose compared to controls. Within the cold-exposed group, BMI, total cholesterol, and the atherogenic coefficient were lower in individuals exposed to low temperatures for a longer time. In conclusion, human PBMC expresses the brown adipocytes marker CIDEA and the browning marker HOXC9, which, varying according to cold-exposure, possibly reflect changes in BAT activation and white fat browning.

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“…A study by Commins et al [ 62 ] showed that administration of exogenous leptin to ob / ob mice resulted in a 4–5-fold increase in mRNA levels of the UCP1 protein in BAT. Efremova et al [ 69 ] found that a constant part of the mediastinal and perirenal fat (up to about 40%) in adult residents of eastern Siberia had the morphology typical of brown adipocytes and that a relevant percentage (up to about 30%) expressed the functional marker of UCP1. This study indicates the possible activation of nonshivering thermogenesis in response to extremely low temperatures in Siberia as part of the evolutionary adaptation mechanism of humans to cold climates.…”

Section: Discussionmentioning

confidence: 99%

The Role of Nonshivering Thermogenesis Genes on Leptin Levels Regulation in Residents of the Coldest Region of Siberia

Nikanorova

Barashkov

Pshennikova

et al. 2021

IJMS

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Leptin plays an important role in thermoregulation and is possibly associated with the microevolutionary processes of human adaptation to a cold climate. In this study, based on the Yakut population (n = 281 individuals) living in the coldest region of Siberia (t°minimum −71.2 °C), we analyze the serum leptin levels and data of 14 single nucleotide polymorphisms (SNPs) of 10 genes (UCP1, UCP2, UCP3, FNDC5, PPARGC1A, CIDEA, PTGS2, TRPV1, LEPR, BDNF) that are possibly involved in nonshivering thermogenesis processes. Our results demonstrate that from 14 studied SNPs of 10 genes, 2 SNPs (the TT rs3811787 genotype of the UCP1 gene and the GG rs6265 genotype of the BDNF gene) were associated with the elevated leptin levels in Yakut females (p < 0.05). Furthermore, of these two SNPs, the rs3811787 of the UCP1 gene demonstrated more indications of natural selection for cold climate adaptation. The prevalence gradient of the T-allele (rs3811787) of UCP1 increased from the south to the north across Eurasia, along the shore of the Arctic Ocean. Thereby, our study suggests the potential involvement of the UCP1 gene in the leptin-mediated thermoregulation mechanism, while the distribution of its allelic variants is probably related to human adaptation to a cold climate.

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A large proportion of mediastinal and perirenal visceral fat of Siberian adult people is formed by UCP1 immunoreactive multilocular and paucilocular adipocytes

Cited by 42 publications

References 39 publications

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Biomarkers of Browning in Cold Exposed Siberian Adults

The Role of Nonshivering Thermogenesis Genes on Leptin Levels Regulation in Residents of the Coldest Region of Siberia

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