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Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction

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Abstract

Despite their critical role in susceptibility to metabolic diseases such as obesity and type 2 diabetes, mechanisms regulating energy balance are extremely complex and far from being fully understood. Both central and peripheral feedback circuits are involved and, despite it was traditionally thought that the energy balance of an organism depends on the equality between calorie intake within the system and energy expenditure, the regulation of energy content in biological systems oversteps the classical physical laws of thermodynamics. The fine-tuned mechanism for body weight and energy storage regulation is aimed to preserve survival chances in response to the variations of energy availability, as expressed by the metabolic flexibility of this system adapting subjects to both starvation and overfeeding. However, these mechanisms can lose their flexibility, with consequent maladaptation to both increased energy intake and calorie restriction leading to the development of several metabolic disturbances.

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Abbreviations

5-HT:

serotonin

α-MSH:

α-melanocyte-stimulating hormone

AgRP:

agouti-related protein

AMP:

adenosine monophosphate

ATP:

adenosine triphosphate

BAT:

brown adipose tissue

BMI:

body mass index

BW:

body weight

CALERIE:

Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy

CNS:

central nervous system

CR:

caloric restriction

CREB:

cAMP response element-binding protein

DiRECT:

DIabetes REmission Clinical Trial

EE:

energy expenditure

EI:

energy intake

FFA:

free fatty acids

FGF-21:

fibroblast growth factor-21

GLP-1:

glucagon-like peptide 1

LCD:

low calorie diet

MC4R:

melanocortin-4 receptor

NPY:

neuropeptide Y

PGC-1α:

peroxisome proliferator-activated receptor gamma coactivator 1-α

POMC:

pro-opiomelanocortin

PPAR-α:

peroxisome proliferator-activated receptor-α

RCT:

randomized controlled trial

REE:

resting energy expenditure

VLCD:

very low calorie diet

WAT:

white adipose tissue

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Correspondence to Roberto Vettor.

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Vettor, R., Di Vincenzo, A., Maffei, P. et al. Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction. Rev Endocr Metab Disord 21, 399–409 (2020). https://doi.org/10.1007/s11154-020-09565-6

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