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Thyroid Axis and Energy Balance: Focus on Animals and Implications for Humankind

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Handbook of Famine, Starvation, and Nutrient Deprivation

Abstract

Research on animals has revealed multiple mechanisms, brain circuits, and peripheral signals that coordinate energy homeostasis. This review summarizes information relevant to the hypothalamic-pituitary-thyroid axis, one of the outputs that the central nervous system uses to control energy utilization. It is hierarchically organized and controlled by paraventricular nucleus hypophysiotropic thyrotropin-releasing hormone neurons integrating central and peripheral information. These neurons regulate thyrotropin secretion from anterior pituitary and thyroid hormone production. Tissue concentrations of thyroid hormones depend in addition on transporters and deiodinases expressed by target tissues. Thyroid hormones control basal metabolic rate, thermogenesis, lipolysis, and glycolysis, as well as the development and performance of immune and nervous systems; they exert feedback control on the axis at multiple levels. Fasting, food restriction, malnutrition, stress, and disease downregulate the activity of the thyroid axis, an adaptation that minimizes energy utilization. In contrast, diet-induced obesity activates the axis, although deiodinase activities limit its capacity to compensate for energy excess. Maternal nutritional status or stress during gestation, and/or lactation, programs offspring’s body weight, neuroendocrine axes, and energy metabolism in the adult. Studies in animals contributed to identify pathophysiological events of the thyroid axis associated with human diseases.

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Abbreviations

Note:

Italics are used for gene or mRNA names, i.e., Trh for animals and TRH for humans, and capital letters, i.e., TRH, for peptides/proteins (HUGO Gene nomenclature Committee; Mouse genome informatics)

11-β-HSD:

11-β hydroxysterol dehydrogenase

3V:

third ventricle

Abd:

abdominal

AC:

adenylyl cyclase

Act:

activity

ACTH:

adrenocorticotropin hormone

AgRP:

agouti-related peptide

Apit:

anterior pituitary

AR:

adrenergic receptor

Arc:

hypothalamic arcuate nucleus

ATP:

adenosine triphosphate

Avp:

arginine vasopressin

BAT:

brown adipose tissue

BBB:

blood–brain barrier

BDNF:

brain–derived neurotrophic factor

BP:

blood pressure

BW:

body weight

CART:

cocaine- and amphetamine-activated transcript

CAs:

catecholamines

Ch:

cholesterol

Cort:

corticosterone

CREB:

cAMP-response element-binding protein

CRH:

corticotropin-releasing hormone

Cx:

cortex

d:

days

db :

diabetes mice

Dio1:

deiodinase type 1

Dio2:

deiodinase type 2

Dio3:

deiodinase type 3

DMN:

hypothalamic dorsomedial nucleus

E:

embryonic

F:

female

FA:

fatty acids

FFA:

free fatty acids

FR:

food restriction

FT3:

free triiodo-L-thyronine

FT4:

free thyroxine

G:

gestation

GABA:

γ-aminobutyric acid

GC:

glucocorticoids

GH:

growth hormone

GR:

glucocorticoid receptor

Gs:

signal-transducing G protein

Hc:

hippocampus

HFD:

high-fat diet

HOMA-IR:

homeostatic model assessment for insulin resistance

HPA:

hypothalamic-pituitary adrenal axis

HPT:

hypothalamic-pituitary-thyroid axis

Ht:

hypothalamus

I− excess + LP:

iodine excess plus a low protein diet

I:

iodine

Ins:

insulin

InsR:

insulin receptor

JAK2:

janus kinase 2

KO:

knockout

L:

lactation

LC:

locus coeruleus

LDL-c:

low-density lipoprotein cholesterol

LH:

lateral hypothalamus

LP:

low protein diet

Lpl:

lipoprotein lipase

LPS:

lipopolysaccharide

M:

male

MBH:

mediobasal hypothalamus

Mc4R:

melanocortin 4 receptor

Mct10:

monocarboxylate transporter 10

Mct8:

monocarboxylate transporter 8

ME:

median eminence

mo:

months old

Mr:

mineralocorticoid receptor

MS:

maternal separation

NE:

norepinephrine

NEFA:

non-esterified fatty acids

NPY:

neuropeptide Y

Nr3c1 :

GR gene

NTIS:

non-thyroidal illness syndrome

NTS:

nucleus tractus solitarius

OATP1C1:

organic anion transporter family member 1C1

Ob :

obese mice

ObRb:

leptin’s receptor b isoform

PD:

postnatal day

Pepck:

phosphoenolpyruvate carboxykinase

Pit:

pituitary

PKA:

protein kinase A

POMC:

proopiomelanocortin

Ppargc1a:

peroxisome proliferator-activated receptor gamma coactivator 1-alpha

PPit:

posterior pituitary

PTU:

propylthiouracil

PVN:

hypothalamic-paraventricular nucleus

RMR:

resting metabolic rate

SCh:

suprachiasmatic nucleus

SOCS3:

suppressor of cytokine signaling 3

STAT3:

signal transducer and activator of transcription 3

T-131I uptake:

thyroid 131iodine uptake

T3:

triiodo-L-thyronine

T4:

thyroxine

TBG:

thyroxine-binding globulin

Tg:

thyroglobulin

TG:

triglyceride

TH:

thyroid hormone

TPO:

thyroid peroxidase

TR or Thr:

thyroid hormone receptor

TRE:

thyroid response element

TRH:

thyrotropin-releasing hormone

TRHDE:

TRH-degrading ectoenzyme

TRHR1:

TRH receptor-1

TSH:

thyrotropin

TSH-R Tshr:

TSH-receptor

TT3:

total triiodo-L-thyronine

TT4:

total thyroxine

UCP1:

uncoupling protein 1

VMN:

hypothalamic ventromedial nucleus

W:

weight

WAT:

white adipose tissue

wk:

week

Y1/Y5R:

NPY receptor-1/5

yrs:

years old

αMSH:

α-melanocyte-stimulating hormone

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Acknowledgments

Supported by grants from CONACYT (CB2015-254960, PN2015-562) and DGAPA-UNAM (IN208515, IN204316, IA200417). The enthusiastic collaboration of our staff and students is deeply recognized; we thank the technical aid of M. Cisneros, F. Romero, S. Ainsworth, and R. Rodríguez. We apologize to authors whose work is cited only in reviews due to space constrains.

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Authors and Affiliations

  1. Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), A.P. 510-3, Cuernavaca, Morelos, 62250, Mexico

    Patricia Joseph-Bravo

  2. Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, 62250, Mexico

    Mariana Gutiérrez-Mariscal, Lorraine Jaimes-Hoy & Jean-Louis Charli

Authors
  1. Patricia Joseph-Bravo
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  2. Mariana Gutiérrez-Mariscal
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  3. Lorraine Jaimes-Hoy
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  4. Jean-Louis Charli
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Corresponding author

Correspondence to Patricia Joseph-Bravo .

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Editors and Affiliations

  1. Diabetes & Nutritional Sci Div Sch, King's College London, London, United Kingdom

    Victor Preedy

  2. Clinical Biochemistry, University of Westminster, Westminster, United Kingdom

    Vinood B. Patel

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Joseph-Bravo, P., Gutiérrez-Mariscal, M., Jaimes-Hoy, L., Charli, JL. (2017). Thyroid Axis and Energy Balance: Focus on Animals and Implications for Humankind. In: Preedy, V., Patel, V. (eds) Handbook of Famine, Starvation, and Nutrient Deprivation. Springer, Cham. https://doi.org/10.1007/978-3-319-40007-5_76-1

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  • DOI: https://doi.org/10.1007/978-3-319-40007-5_76-1

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  • Print ISBN: 978-3-319-40007-5

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