Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice.
Mol Metab
; 6(8): 854-862, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28752049
ABSTRACT
OBJECTIVE:
We have previously shown that the consumption of a low-carbohydrate ketogenic diet (KD) by mice leads to a distinct physiologic state associated with weight loss, increased metabolic rate, and improved insulin sensitivity [1]. Furthermore, we identified fibroblast growth factor 21 (FGF21) as a necessary mediator of the changes, as mice lacking FGF21 fed KD gain rather than lose weight [2]. FGF21 activates the sympathetic nervous system (SNS) [3], which is a key regulator of metabolic rate. Thus, we considered that the SNS may play a role in mediating the metabolic adaption to ketosis.METHODS:
To test this hypothesis, we measured the response of mice lacking all three ß-adrenergic receptors (ß-less mice) to KD feeding.RESULTS:
In contrast to wild-type (WT) controls, ß-less mice gained weight, increased adipose tissue depots mass, and did not increase energy expenditure when consuming KD. Remarkably, despite weight-gain, ß-less mice were insulin sensitive. KD-induced changes in hepatic gene expression of ß-less mice were similar to those seen in WT controls eating KD. Expression of FGF21 mRNA rose over 60-fold in both WT and ß-less mice fed KD, and corresponding circulating FGF21 levels were 12.5 ng/ml in KD-fed wild type controls and 35.5 ng/ml in KD-fed ß-less mice.CONCLUSIONS:
The response of ß-less mice distinguishes at least two distinct categories of physiologic effects in mice consuming KD. In the liver, KD regulates peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways through an action of FGF21 independent of the SNS and beta-adrenergic receptors. In sharp contrast, induction of interscapular brown adipose tissue (BAT) and increased energy expenditure absolutely require SNS signals involving action on one or more ß-adrenergic receptors. In this way, the key metabolic actions of FGF21 in response to KD have diverse effector mechanisms.Palavras-chave
BAT, brown adipose tissue; EE, energy expenditure; FGF21, fibroblast growth factor 21; IP, intraperitoneal; ITT, insulin tolerance test; IWAT, inguinal white adipose tissue; KD, ketogenic diet; Ketogenic diet; PPARα, peroxisome proliferator-activated receptor alpha; SEM, standard error of the mean; SNA, sympathetic nerve activity; SNS, sympathetic nervous system; Sympathetic nervous system; UCP1, uncoupling protein 1; Weight loss; ß-Adrenergic receptors; ß-less, lacking ß1, ß2, ß3 adrenergic receptors
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adaptação Fisiológica
/
Redução de Peso
/
Receptores Adrenérgicos
/
Dieta Cetogênica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Metab
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos