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Human Brown Adipose Tissues

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (10 May 2022) | Viewed by 33472

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Dr. Kumiko Saeki

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Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Interests: regenerative medicine; human pluripotent stem cells; brown adipose tissue; metabolism; batokines

Special Issue Information

Dear Colleagues,

The presence of brown adipose tissue (BAT) in adult humans was described as early as 1908 in autopsy reports by Edmond Bonnot. In his paper, interscapular BAT was mentioned as the interscapular gland, which has processes in cervical, clavicular, and scapular regions. More than one hundred years later, the human BATs were rediscovered, triggered by the fact that healthy individuals unexpectedly showed radioactive signals in cervical and supraclavicular regions in ¹⁸F-FDG-PET examinations and confirmed by histological and gene expression analyses. Under physiological conditions, the activities of human BATs are augmented by cold stimuli, beta3-adrenergic signals, and atrial natriuretic peptide. Pathological conditions such as cancer cachexia can induce hyperactivation of BATs although the critical mediators for cachexia induction remain undetermined. BATs secret various bioactive substances as generally termed as BATokines. Despite several reports regarding the candidate molecules, their main producers are not BATs per se in most cases, and therefore, there may be still undiscovered BATokines that play crucial roles in metabolism regulation. Since there is a large hurdle in obtaining high-quality human BAT samples from technical and ethical points of view, human pluripotent stem cells(hPSC)-derived brown adipocytes (BA) have been providing a beneficial tool to study human BATs. To solve the mysteries of human BATs, findings obtained from animal experiments, clinical research, and hPSC-derived BA-based studies should effectively be integrated in tight collaboration among researchers.

Dr. Kumiko Saeki
Guest Editor

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Keywords

Brown adipose tissue
Human embryonic stem (ES) cells/iPS cells
BATokines
Extracellular vesicles
Imaging

Published Papers (3 papers)

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Research

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22 pages, 4932 KiB

Open AccessFeature PaperArticle

Differential Effects of 25-Hydroxyvitamin D₃ versus 1α 25-Dihydroxyvitamin D₃ on Adipose Tissue Browning in CKD-Associated Cachexia

by Robert H. Mak, Uwe Querfeld, Alex Gonzalez, Sujana Gunta and Wai W. Cheung

Cells 2021, 10(12), 3382; https://doi.org/10.3390/cells10123382 - 1 Dec 2021

Cited by 4 | Viewed by 1876

Abstract

Patients with chronic kidney disease (CKD) often have low serum concentrations of 25(OH)D₃ and 1,25(OH)₂D₃. We investigated the differential effects of 25(OH)D₃ versus 1,25(OH)₂D₃ repletion in mice with surgically induced CKD. Intraperitoneal supplementation of 25(OH)D₃ (75 μg/kg/day) or 1,25(OH)₂D₃ (60 ng/kg/day) for 6 weeks normalized serum 25(OH)D₃ or 1,25(OH)₂D₃ concentrations in CKD mice, respectively. Repletion of 25(OH)D₃ normalized appetite, significantly improved weight gain, increased fat and lean mass content and in vivo muscle function, as well as attenuated elevated resting metabolic rate relative to repletion of 1,25(OH)₂D₃ in CKD mice. Repletion of 25(OH)D₃ in CKD mice attenuated adipose tissue browning as well as ameliorated perturbations of energy homeostasis in adipose tissue and skeletal muscle, whereas repletion of 1,25(OH)₂D₃ did not. Significant improvement of muscle fiber size and normalization of fat infiltration of gastrocnemius was apparent with repletion of 25(OH)D₃ but not with 1,25(OH)₂D₃ in CKD mice. This was accompanied by attenuation of the aberrant gene expression of muscle mass regulatory signaling, molecular pathways related to muscle fibrosis as well as muscle expression profile associated with skeletal muscle wasting in CKD mice. Our findings provide evidence that repletion of 25(OH)D₃ exerts metabolic advantages over repletion of 1,25(OH)₂D₃ by attenuating adipose tissue browning and muscle wasting in CKD mice. Full article

(This article belongs to the Special Issue Human Brown Adipose Tissues)

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18 pages, 1985 KiB

Open AccessArticle

A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia

by Alex Gonzalez, Wai W. Cheung, Elliot A. Perens, Eduardo A. Oliveira, Arieh Gertler and Robert H. Mak

Cells 2021, 10(8), 1954; https://doi.org/10.3390/cells10081954 - 31 Jul 2021

Cited by 10 | Viewed by 3028

Abstract

Mice lacking the functional cystinosin gene (Ctns^−/−), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns^−/− mice. We treated 12-month-old Ctns^−/− mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns^−/− mice. PLA attenuated adipose tissue browning in Ctns^−/− mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns^−/− mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns^−/− mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns^−/− mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC. Full article

(This article belongs to the Special Issue Human Brown Adipose Tissues)

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Review

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23 pages, 1187 KiB

Open AccessFeature PaperReview

Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

by Rajan Singh, Albert Barrios, Golnaz Dirakvand and Shehla Pervin

Cells 2021, 10(11), 3030; https://doi.org/10.3390/cells10113030 - 5 Nov 2021

Cited by 38 | Viewed by 27578

Abstract

Obesity-associated metabolic abnormalities comprise a cluster of conditions including dyslipidemia, insulin resistance, diabetes and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from the accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. A variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago, and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. A substantially decreased BAT activity in individuals with obesity indicates a role for BAT in the setting of human obesity. On the other hand, BAT mass and its prevalence correlate with lower body mass index (BMI), decreased age and lower glucose levels, leading to a lower incidence of cardio-metabolic diseases. The increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. A deeper understanding of the role of BAT in human metabolic health and its interrelationship with body fat distribution and deciphering proper strategies to increase energy expenditure, by either increasing functional BAT mass or inducing white adipose browning, holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders. Full article

(This article belongs to the Special Issue Human Brown Adipose Tissues)

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