TY - JOUR
T1 - Obesity I
T2 - Overview and molecular and biochemical mechanisms
AU - Lustig, Robert H.
AU - Collier, David
AU - Kassotis, Christopher
AU - Roepke, Troy A.
AU - Ji Kim, Min
AU - Blanc, Etienne
AU - Barouki, Robert
AU - Bansal, Amita
AU - Cave, Matthew C.
AU - Chatterjee, Saurabh
AU - Choudhury, Mahua
AU - Gilbertson, Michael
AU - Lagadic-Gossmann, Dominique
AU - Howard, Sarah
AU - Lind, Lars
AU - Tomlinson, Craig R.
AU - Vondracek, Jan
AU - Heindel, Jerrold J.
N1 - Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the “obesogen hypothesis” (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.
AB - Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the “obesogen hypothesis” (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.
KW - Adipose tissue
KW - Energy balance
KW - Hormone receptors
KW - Metabolism
KW - Microbiome
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85129616235&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2022.115012
DO - 10.1016/j.bcp.2022.115012
M3 - Review article
SN - 0006-2952
VL - 199
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
M1 - 115012
ER -