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Understanding the molecular mechanisms and role of autophagy in obesity

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Abstract

Vital for growth, proliferation, subsistence, and thermogenesis, autophagy is the biological cascade, which confers defence against aging and various pathologies. Current research has demonstrated de novo activity of autophagy in stimulation of biological events. There exists a significant association between autophagy activation and obesity, encompassing expansion of adipocytes which facilitates β cell activity. The main objective of the manuscript is to enumerate intrinsic role of autophagy in obesity and associated complications. The peer review articles published till date were searched using medical databases like PubMed and MEDLINE for research, primarily in English language. Obesity is characterized by adipocytic hypertrophy and hyperplasia, which leads to imbalance of lipid absorption, free fatty acid release, and mitochondrial activity. Detailed evaluation of obesity progression is necessary for its treatment and related comorbidities. Data collected in regard to etiological sustaining of obesity, has revealed hypothesized energy misbalance and neuro-humoral dysfunction, which is stimulated by autophagy. Autophagy regulates chief salvaging events for protein clustering, excessive triglycerides, and impaired mitochondria which is accompanied by oxidative and genotoxic stress in mammals. Autophagy is a homeostatic event, which regulates biological process by eliminating lethal cells and reprocessing physiological constituents, comprising of proteins and fat. Unquestionably, autophagy impairment is involved in metabolic syndromes, like obesity. According to an individual’s metabolic outline, autophagy activation is essential for metabolism and activity of the adipose tissue and to retard metabolic syndrome i.e. obesity. The manuscript summarizes the perception of current knowledge on autophagy stimulation and its effect on the obesity.

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Abbreviations

ACE:

Angiotensin converting enzyme

AF:

Atrial fibrillation

AgRP:

agouti-related protein

AMPK:

5' AMP-activated protein kinase

AT1:

Angiotensin 1

Atg1:

Autophagy associated protein 1

ATP:

Adenosine triphosphate

BAT:

Brown adipose tissue

CMA:

Chaperone-mediated autophagy

DAPK:

Death-associated protein kinase

DM:

Diabetes mellitus

ER:

Endoplasmic reticulu

ERK:

Extracellular signal-regulated kinases

FFAs:

Free fatty acids

GAIP:

G α interacting protein

GTP:

Guanosine-5'-triphosphate

HFD:

High-fat diet

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

iNOS:

Inducible nitric oxide synthase

IRSs:

Insulin receptor substrates

JNK:

c-Jun N-terminal kinase

LAP:

LC3-associated phagocytosis

LC3:

Light chain 3

LDL:

Low-density lipoprotein

mTOR:

Mammalian target of rapamycin

NAD+:

Nicotinamide adenine dinucleotide

NF-κb:

Nuclear factor-kappa B

NO:

Nitric oxide

OS:

Oxidative stress

p38 MAPK:

P38 mitogen-activated protein kinases

PDK1:

Phosphoinositide-dependent kinase-1

Pdx1:

Pancreatic and duodenal homeobox 1

PIP3:

Phosphatidylinositol 3,4,5-triphosphate

PI3K:

Phosphoinositide 3-kinase

POMC:

Proopiomelanocortin;

PTEN:

Phosphatase and tensin homolog

RAS:

Renin-angiotensin system

ROS:

Reactive oxygen species

SIRT:

Sirtuin

STAT-1:

Signal transducer and activator of transcription 1

TNFα:

Tumour necrosis factor-α

TORC:

Target of rapamycin complex

TSC2:

Tuberous sclerosis complex 2

UCP1:

Uncoupling protein 1

ULK1:

Unc-51 Like Autophagy Activating Kinase 1

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Acknowledgement

The authors want to thank Chitkara College of Pharmacy, Chitkara University, Punjab, India for providing resources for completion of the current article.

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  1. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Tapan Behl, Aayush Sehgal, Rajni Bala & Swati Chadha

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  1. Tapan Behl
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  2. Aayush Sehgal
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  3. Rajni Bala
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  4. Swati Chadha
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TB: Conceived the idea and wrote the draft of the article; AS and SC: Literature Review; RB: Figure Work.

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Correspondence to Tapan Behl.

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Behl, T., Sehgal, A., Bala, R. et al. Understanding the molecular mechanisms and role of autophagy in obesity. Mol Biol Rep 48, 2881–2895 (2021). https://doi.org/10.1007/s11033-021-06298-w

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