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The Pathophysiology of Obesity and Obesity-Related Disease

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The ASMBS Textbook of Bariatric Surgery

Abstract

Body weight is controlled by physiologic systems that regulate food intake, metabolic rate, and multiple other metabolic functions. These physiologic systems have been selected over eons of human evolution in a nutrient-poor environment, imparting a selective advantage in the form of metabolic thrift. Metabolic thrift causes a blossoming of the obesity phenotype in a modern nutrient-rich obesogenic environment. Adipose tissue acts as a buffer for high-energy nutrients and metabolites, protecting other tissues from nutrient excess and nutrient toxicity. Metabolic disease results from a failure of adipose tissue nutrient buffering capacity due to chronic delivery of excess nutrients to adipocytes, which in turn leads to nutrient overflow into the systemic circulation. Resulting nutrient toxicity in virtually all peripheral tissues generates complex cell stress responses that underlie the pathogenesis of metabolic disease, a diverse set of pathologies that involve every organ system.

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Abbreviations

AgRP:

Agouti-related peptide

ARCN:

Arcuate nucleus

ATM:

Adipose tissue macrophages

BAT:

Brown adipose tissue

BMI:

Body mass index

CART:

Cocaine- and amphetamine-regulated transcript

CNS:

Central nervous system

DIT:

Diet-induced thermogenesis

ER:

Endoplasmic reticulum

GIP:

Glucose-dependent insulinotropic polypeptide

GLP-1:

Glucagon-like peptide-1

GWAS:

Genome-wide association analysis

HFC:

Hypothalamic feeding center

LCFA:

Long-chain fatty acids

LHA:

Lateral hypothalamic area

MAPK:

Mitogen-activated protein kinases

MCH:

Melanin-concentrating hormone

MSH:

Melanocyte stimulating hormone

NAFLD:

Nonalcoholic fatty liver disease

NEAT:

Non-exercise-induced thermogenesis

NO:

Nitric oxide

NPY:

Neuropeptide Y

NREE:

Non-resting energy expenditure

POMC:

Pro-opiomelanocortin

PUFA:

Polyunsaturated fatty acids

PVN:

Paraventricular nucleus

REE:

Resting energy expenditure

ROS:

Reactive oxygen species

SAT:

Subcutaneous adipose tissue

SNP:

Single nucleotide polymorphism

SVF:

Stromal-vascular cell fraction

TEE:

Total energy expenditure

UCP:

Uncoupling proteins

UPR:

Unfolded protein response

VAT:

Visceral adipose tissue

WAT:

White adipose tissue

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Authors and Affiliations

  1. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Robert W. O’Rourke

  2. Bariatric Surgery Program, Division of General Surgery, Ann Arbor Veterans Administration Hospital, Ann Arbor, MI, USA

    Robert W. O’Rourke

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  1. Robert W. O’Rourke
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Correspondence to Robert W. O’Rourke .

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Editors and Affiliations

  1. Department of Surgery, Division of Gastrointestinal Surgery, University of California, Irvine Medical Center, Orange, CA, USA

    Ninh T. Nguyen

  2. Department of Surgery, The Ohio State University, Columbus, OH, USA

    Stacy A. Brethauer

  3. Bariatric and Minimally Invasive Surgery Division, Yale School of Medicine, New Haven, CT, USA

    John M. Morton

  4. Bariatric Surgery, Metabolic and Bariatric Care, CHI Memorial Hospital, Chattanooga, TN, USA

    Jaime Ponce

  5. Department of General Surgery, The Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, FL, USA

    Raul J. Rosenthal

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O’Rourke, R.W. (2020). The Pathophysiology of Obesity and Obesity-Related Disease. In: Nguyen, N., Brethauer, S., Morton, J., Ponce, J., Rosenthal, R. (eds) The ASMBS Textbook of Bariatric Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-27021-6_2

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