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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Joseph-Bravo, P., Gutiérrez-Mariscal, M., Jaimes-Hoy, L., Charli, JL. (2019). 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/10.1007/978-3-319-55387-0_76
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