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Recent advances in human brown fat physiology

Muralidhara DV, Muralidhara KD

Indian J. Physiol. Pharmacol., 2011 Jul-Sep;55(3):197-206.
PMID: 22471225

Of the two variants of adipose tissue, white fat is traditionally known as a lipid rich tissue which undergoes pathological expansion in obese conditions. To counter the excess accumulation of white fat in states of energy imbalance, the second and unique type of brown fat plays a key role by burning extra energy into heat through a special metabolic pathway. In addition brown fat also plays a vital role in thermoregulation in animals and newborn humans and infants. Recent progress in research areas of these two types of fat tissue has provided compelling evidence to show that they secrete a large number of chemicals that play an important role in body weight control that involves several mechanisms. Brown fat was considered absent in the adult humans until recently. But new techniques have provided ample support for its active existence. Based on the very recent data it has been suggested that brown fat can be a target organ in the treatment of obesity which can lead to exciting and informative outcomes in the future.

Matched MeSH terms: Adipose Tissue, Brown/physiology*
Heat stress reduces brown adipose tissue activity by exacerbating mitochondrial damage in type 2 diabetic mice

Lai P, Zhang L, Qiu Y, Ren J, Sun X, Zhang T, et al.

J Therm Biol, 2024 Jan;119:103799.
PMID: 38342042 DOI: 10.1016/j.jtherbio.2024.103799

Epidemiological evidence shows that diabetic patients are susceptible to high temperature weather, and brown adipose tissue (BAT) activity is closely related to type 2 diabetes (T2DM). Activation of BAT under cold stress helps improve T2DM. However, the impact of high temperature on the activity of BAT is still unclear. The study aimed to investigate the impact of heat stress on glucose and lipid metabolism in T2DM mice by influencing BAT activity. High-fat feeding and injecting streptozotocin (STZ) induced model of T2DM mice. All mice were randomly divided into three groups: a normal(N) group, a diabetes (DM) group and a heat stress diabetes (DMHS) group. The DMHS group received heat stress intervention for 3 days. Fasting blood glucose, fasting serum insulin and blood lipids were measured in all three groups. The activity of BAT was assessed by using quantitative real-time PCR (qRT-PCR), electron microscopy, and PET CT. Furthermore, the UHPLC-Q-TOF MS technique was employed to perform metabolomics analysis of BAT on both DM group and DMHS group. The results of this study indicated that heat stress aggravated the dysregulation of glucose and lipid metabolism, exacerbated mitochondrial dysfunction in BAT and reduced the activity of BAT in T2DM mice. This may be related to the abnormal accumulation of branched-chain amino acids (BCAAs) in the mitochondria of BAT.

Matched MeSH terms: Adipose Tissue, Brown/metabolism
Murine in vitro cellular models to better understand adipogenesis and its potential applications

Vohra MS, Ahmad B, Serpell CJ, Parhar IS, Wong EH

Differentiation, 2020 08 23;115:62-84.
PMID: 32891960 DOI: 10.1016/j.diff.2020.08.003

Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology.

Matched MeSH terms: Adipose Tissue, Brown/growth & development; Adipose Tissue, Brown/metabolism*
Brown/Beige adipose tissues and the emerging role of their secretory factors in improving metabolic health: The batokines

Ahmad B, Vohra MS, Saleemi MA, Serpell CJ, Fong IL, Wong EH

Biochimie, 2021 May;184:26-39.
PMID: 33548390 DOI: 10.1016/j.biochi.2021.01.015

Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.

Matched MeSH terms: Adipose Tissue, Brown/metabolism*; Adipose Tissue, Brown/pathology
Fulltext A rare case of retropharyngeal hibernoma

Nazli Z, Norizal MN, Noor Kaslina MK, Abdul Fattah AW

Med J Malaysia, 2015 Apr;70(2):98-9.
PMID: 26162385 MyJurnal

Hibernoma is a slow growing, rare benign tumour, which derived from brown adipose tissue. This tumour is usually found in the area where foetal fat persists such as back, axilla, retro peritoneum and thorax. Hibernoma rarely occurs in the retro pharynx. We report a case of retropharyngeal hibernoma in a 44-year-old male. He presented with obstructive symptoms for six months and a retropharyngeal mass upon examination. His CT scan findings showed a mass in the prevertebral region from level of C2 until C5 causing narrowing of upper aero digestive tract. Histopathological examination reported as hibernoma.

Matched MeSH terms: Adipose Tissue, Brown
Fulltext Novel discovery of Averrhoa bilimbi ethanolic leaf extract in the stimulation of brown fat differentiation program in combating diet-induced obesity

Lau WK, Noruddin NAA, Ariffin AH, Mahmud MZ, Noor MHM, Amanah A, et al.

BMC Complement Altern Med, 2019 Sep 05;19(1):243.
PMID: 31488120 DOI: 10.1186/s12906-019-2640-3

BACKGROUND: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of metabolic disorders including diabetes mellitus, hypertension and obesity. The present study aims to investigate the browning activity on white adipocytes by A. bilimbi leaf extract and to evaluate the potential mechanisms.
METHODS: Ethanolic leaf extract of A. bilimbi was exposed to Myf5 lineage precursor cells to stimulate adipocyte differentiation. Protein expressions of brown adipocyte markers were determined through high content screening analysis and validated through western blotting. Mito Stress Test assay was conducted to evaluate the cellular oxygen consumption rate upon A. bilimbi treatment.
RESULTS: A. bilimbi ethanolic leaf extract exhibited an adipogenesis effect similar to a PPARgamma agonist. It also demonstrated brown adipocyte differentiation in myoblastic Myf5-positive precursor cells. Expression of UCP1 and PRDM16 were induced. The basal metabolic rate and respiratory capacity of mitochondria were increased upon A. bilimbi treatment.
CONCLUSIONS: The findings suggest that Averrhoa bilimbi ethanolic leaf extract induces adipocyte browning through PRDM16 activation and enhances mitochondria activity due to UCP1 up-regulation.

Matched MeSH terms: Adipose Tissue, Brown/cytology; Adipose Tissue, Brown/drug effects*; Adipose Tissue, Brown/metabolism
Fulltext Effect of brown adipose tissue activation on myocardial fluorine-18-fluorodeoxyglucose uptake

Alenezi SA, Dannoon SF, Alnafisi NS, Asa'ad SM, Osman MM, Elgazzar AH

World J Nucl Med, 2020 01 14;19(1):41-46.
PMID: 32190021 DOI: 10.4103/wjnm.WJNM_16_19

The aim of this study is to investigate the relationship between brown adipose tissue (BAT) activation and myocardial fluorine-18-fluorodeoxyglucose ([18F] FDG) uptake in terms of intensity and patterns. The patients were divided into two groups as follows: BAT and control groups. The BAT group consists of 34 cases that showed BAT uptake. The control group, with no BAT uptake, included 68 patients who were matched for body mass index, gender, and season. The scans were retrospectively reviewed by two nuclear medicine physicians who visually evaluated the intensity of myocardial [18F] FDG uptake. The myocardial [18F] FDG uptake was visually classified into the following three patterns: diffuse, heterogeneous, and focal. The regions of activated BAT distribution were noted. The mean myocardial [18F] FDG uptake was 2.50 ± 0.75 for the BAT group and 2.13 ± 0.88 for the control group with a statistically significant difference (P = 0.031). The myocardial [18F] FDG uptake pattern was similar in the BAT and control groups with the diffuse pattern being the most common, followed by the heterogeneous and less commonly focal. In the BAT group, the anatomical distribution of BAT was mainly in supraclavicular, paravertebral, and axillary and to a lesser extent in cervical regions. BAT group had a significantly higher intensity of [18F] FDG myocardial uptake compared to that of the control group. The presence of activated BAT did not affect the pattern of myocardial uptake. Knowledge of these findings may help in understanding the variability of myocardial [18F] FDG uptake and consequently in avoiding misinterpretation of cardiac findings in positron-emission tomography/computed tomography studies.

Matched MeSH terms: Adipose Tissue, Brown
Fulltext Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Ahmad B, Serpell CJ, Fong IL, Wong EH

Front Mol Biosci, 2020;7:76.
PMID: 32457917 DOI: 10.3389/fmolb.2020.00076

Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis - it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics.

Matched MeSH terms: Adipose Tissue, Brown
Fulltext Pathological findings in a mouse model for Coxsackievirus A16 infection

Hooi, Yuan Teng, Ong, Kien Chai, Perera, David, Wong, Kum Thong

Neurology Asia, 2015;20(4):343-347.
MyJurnal

Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually
presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported
to cause severe and fatal neurological complications but little is known about these complications.
In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical
strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including
reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically,
the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In
the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons
in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is
very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by
the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary
pathological findings indicate that our mouse models can be further developed to be useful models
for pathogenesis studies, and vaccine and anti-viral drug evaluation.

Matched MeSH terms: Adipose Tissue, Brown