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Role of Distinct Fat Depots in Metabolic Regulation and Pathological Implications

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Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 186))

Abstract

People suffering from obesity and associated metabolic disorders including diabetes are increasing exponentially around the world. Adipose tissue (AT) distribution and alteration in their biochemical properties play a major role in the pathogenesis of these diseases. Emerging evidence suggests that AT heterogeneity and depot-specific physiological changes are vital in the development of insulin resistance in peripheral tissues like muscle and liver. Classically, AT depots are classified into white adipose tissue (WAT) and brown adipose tissue (BAT); WAT is the site of fatty acid storage, while BAT is a dedicated organ of metabolic heat production. The discovery of beige adipocyte clusters in WAT depots indicates AT heterogeneity has a more central role than hither to ascribed. Therefore, we have discussed in detail the current state of understanding on cellular and molecular origin of different AT depots and their relevance toward physiological metabolic homeostasis. A major focus is to highlight the correlation between altered WAT distribution in the body and metabolic pathogenesis in animal models and humans. We have also underscored the disparity in the molecular (including signaling) changes in various WAT tissues during diabetic pathogenesis. Exercise-mediated beneficial alteration in WAT physiology/distribution that protects against metabolic disorders is evolving. Here we have discussed the depot-specific biochemical adjustments induced by different forms of exercise. A detailed understanding of the molecular details of inter-organ crosstalk via substrate utilization/storage and signaling through chemokines provide strategies to target selected WAT depots to pharmacologically mimic the benefits of exercise countering metabolic diseases including diabetes.

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Abbreviations

AgRP:

Agouti-related peptide

AKT1:

A strain k thymoma/transforming protein kinase 1

ANF:

Atrial natriuretic factor

ANGPTL4:

Angiopoietin-like 4

ANP:

Atrial natriuretic peptide

ARC:

Arcuate nucleus

AT:

Adipose tissue

BAIBA:

β-aminoisobutyric acid

BAT:

Brown adipose tissue

BCAAs:

Branched-chain amino acids

BDNF:

Brain-derived neurotrophic factor

BMP:

Bone morphogenetic protein

BNP:

B-type natriuretic peptide

C/EBP:

CCAAT/enhancer binding proteins

CAR4:

Carbonic anhydrase

CD:

Cluster of differentiation

CIDEA:

Cell death-inducing DFFA-like effector A

CNS:

Central nervous system

Cox:

Cytochrome c oxidase

DAG:

Diacylglycerol

dsWAT:

Deep subcutaneous WAT

Ear2:

Eosinophil-associated ribonuclease A-2

EBF:

Empty body fat

EGR1:

Early growth response 1

EN1:

Engrailed-1

Epsti1:

Epithelial stromal interaction 1

Eva1:

Epithelial V-like antigen 1

eWAT:

Epididymal white adipose tissue

EWS:

Ewing sarcoma

FGF9:

Fibroblast growth factor 9

FNDC4:

Fibronectin type III domain-containing 4

FOXC2:

Forkhead box C2

FSP27:

Fat-specific protein 27

GDF15:

Growth differentiation factor 15

GLUT1:

Glucose transporter protein type 1

GPR:

G-protein coupled receptor

Grb10:

Growth factor receptor bound protein 10

GSK-3:

Glycogen synthase kinase 3

HIF1:

Hypoxia-inducible factor

HSL:

Hormone-sensitive lipase

Hspb1:

Small heat shock protein beta-1

hTBC1:

Human TBC1 isoform

IKK:

IκB kinase

IL6:

Interleukin 6

ILC2:

Innate lymphoid type 2 cells

InR:

Insulin resistance

IR:

Insulin receptor

IRE1α:

Inositol-requiring transmembrane kinase endoribonuclease-1α

IRF 4:

Interferon regulatory factor 4

IRS-2:

IR substrate 2

iWAT:

Inguinal WAT

JNK:

c-Jun N-terminal kinase

KLF11:

Kruppel-like factor 11

LHX8:

LIM Homeobox8

MCP-1:

Monocyte chemoattractant protein-1

MEK:

Mitogen-activated protein kinase

Met-Enk:

Methionine-enkephalin

METRNL:

Meteorin-like hormone

MSCs:

Mesenchymal stem cells

mTOR:

Mechanistic target of rapamycin

Myf5:

Myogenic factor 5

MyoD:

Myoblast determination protein

NE:

Norepinephrine

NRG-4:

Neuregulin 4

OGT:

O-GlcNAc transferase

P2RX5:

P2X purinoceptor5

PAI-1:

Plasminogen activator inhibitor 1

PAT:

Phosphate acetyl transferase

PAX7:

Paired box gene 7 protein

PDGFR:

Platelet-derived growth factor receptor

PEDF:

Pigment epithelium-derived factor

PEPCK:

Phosphoenol pyruvate carboxy kinase

PERK:

PKR-like ER protein kinase

PET:

Positron emission tomography

PGC1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PI3K:

Phosphoinositide 3-kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

POMC:

Proopiomelanocortin

PRDM:

PR domain zinc finger protein

PTEN:

Phosphatase and tensin homolog

ROS:

Reactive oxygen species

RyR:

Ryanodine receptor

S6K:

S6 kinase beta-1

SERCA:

Sarco/endoplasmic reticulum Ca2+-ATPase

SFRP4:

Secreted frizzled-related protein 4

SFRP5:

Soluble frizzled-related protein 5

SHIP:

SH2 domain-containing inositol 5-phosphatases

SkM:

Skeletal muscle

SLC25A44:

Solute carrier family 25 member 44

SOCS:

Suppressor of cytokine signaling

SP100:

Sp100 nuclear antigen

TAF7L:

TATA-binding protein-associated factor 7L

Tcf7l:

T-cell-specific factor 7 like 1

Tfam:

Mitochondrial transcription factor A

TGF-β:

Transforming growth factor beta

TLR:

Toll like receptor

TMEM26:

Transmembrane protein 26

TNFSF14:

Tumor necrosis factor superfamily member14

TNFα:

Tumor necrosis factor α

UCP1:

Uncoupling protein 1

VEGF-A:

Vascular endothelial growth factor A

WAT:

White adipose tissue

WISP:

WNT1-inducible signaling pathway protein

WNT:

Wingless-related integration site

YBX1:

Y-box binding protein 1

ZFP:

Zinc finger protein

ZIC1:

Zinc finger protein of the cerebellum 1

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Acknowledgments

We thank Punyadhara Pani, Gourabmani Swalsingh, and Sunil Pani for constructive critical suggestions and discussions that helped us to shape this manuscript.

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Authors and Affiliations

  1. School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India

    Bijayashree Sahu, Ojas Tikoo, Benudhara Pati, Unmod Senapati & Naresh C. Bal

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  1. Bijayashree Sahu
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  2. Ojas Tikoo
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Correspondence to Naresh C. Bal .

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  1. Department of Biology, University of Copenhagen, Copenhagen, Denmark

    Stine Helene Falsig Pedersen

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Author Contributions

BS and NCB conceived the idea. BS, OT, and the US prepared the first draft and figures. All authors critically discussed and edited the manuscript.

Data Availability Statement

Data sharing does not apply to this article as no new data were created or analyzed in this study.

Funding

This work was supported by the Council of Scientific and Industrial Research (CSIR), India (file no.09/1035 (0011)/2017-EMR-I to BS for Junior Research Fellowship), the Science and Engineering Research Board (SERB), DST, India (Grant number ECR/2016/001247 to NCB), and DBT, India (Grant number BT/RLF/Re-entry/41/2014 and BT/PR28935/MED/30/2035/2018).

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Sahu, B., Tikoo, O., Pati, B., Senapati, U., Bal, N.C. (2022). Role of Distinct Fat Depots in Metabolic Regulation and Pathological Implications. In: Pedersen, S.H.F. (eds) Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 186. Springer, Cham. https://doi.org/10.1007/112_2022_73

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