mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
- University of Cambridge, United Kingdom
- The Albert Einstein College of Medicine, United States
Figures
Figure 1 with 1 supplement
AGRP neurons control iBAT thermogenesis.
iBAT temperature (a), energy expenditure (b), locomotor activity (c), Norepinephrine turnover (n = 8) (d) and phosphorylation levels of lipolytic pathways in the iBAT (d) following chemogenetic …
Figure 1—figure supplement 1
AGRP neurons control iBAT thermogenesis.
Confirmation of successful AAV-targeting using mCherry staining - Scale bar 150 μm (a). Confirmation of increased food intake upon CNO administration (b) iBAT temperature in response to local …
Figure 2 with 1 supplement
Food availability and sensory cues of food availability modulate the AGRP-iBAT circuit.
iBAT temperature (a), energy expenditure (b) and locomotor activity (c) following chemogenetic activation of AGRP neurons in the presence of food (DESIGN 2). iBAT temperature (d), energy expenditure …
Figure 2—figure supplement 1
Food availability and sensory cues of food availability modulate the AGRP-iBAT circuit.
iBAT temperature (a) and energy expenditure (b) following chemogenetic activation of AGRP neurons and exposure to a novel empty container. Data are mean ± SEM.
Figure 3 with 1 supplement
mTOR signaling in AGRP neurons senses endogenous and environmental signals of energy availability, regulates AGRP activity and iBAT thermogenesis.
Activation levels of mTOR in Npy-GFP neurons following a 18 hr fast and 1 hr chow re-feed (a, d, n = 5), and a 48 hr transition from chow to HF diet (b, e, n = 6), and a 18 hr fast followed by a 30 …
Figure 3—figure supplement 1
mTOR signaling in AGRP neurons senses endogenous and environmental signals of energy availability, regulates AGRP activity and iBAT thermogenesis.
iBAT temperature (a) and energy expenditure (b) in mice fasted for 19 hr and refed for 60 min. p-mTOR immunofluorescent staining in mouse hypothalamic brain sections at the rostrocaudal level of the …
Figure 4 with 1 supplement
Metabolic phenotyping of mice expressing constitutively active mutant of mTORC1 effector p70 S6 kinase one in Agrp-IRES-cre (Agrp-CA-S6) or wild-type (WT-CA-S6) littermates.
Food intake (a), body weight gain on high-fat diet (b), energy expenditure (c), RER (d), locomotor activity (e), iBAT temperature (f), iBAT thermogenic gene expression (g), iBAT temperature …
Figure 4—figure supplement 1
Metabolic phenotyping of mice expressing constitutively active mutant of mTORC1 effector p70 S6 kinase one in Agrp-IRES-cre (Agrp-CA-S6) or wild-type (WT-CA-S6) littermates.
Ha (a) and p-rpS6 (b) immunostaining in Agrp-IRES-cre;Npy-GFP mice infected with the pCDH-CMV-FLEX-HA-S6K1-F5a lentivirus. Body weight gain (c) fat mass (d) and glucose tolerance (d) of Agrp-CA-S6 …
Figure 5 with 1 supplement
Metabolic phenotyping of mice expressing dominant negative mutant of mTORC1 effector p70 S6 kinase 1 (S6K1) in Agrp-IRES-cre (Agrp-DN-S6) or wild-type (WT-DN-S6).
Energy expenditure (a), locomotor activity (b), iBAT temperature (c), iBAT thermogenic gene expression (d), body weight gain during initial switch to HF diet (e), food intake (f), body weight loss …
Figure 5—figure supplement 1
Metabolic phenotyping of mice expressing dominant negative mutant of mTORC1 effector p70 S6 kinase 1 (S6K1) in Agrp-IRES-cre(Agrp-DN-S6) or wild-type (WT-DN-S6).
Ha (a) and p-rpS6 (b) immunostaining in Agrp-IRES-cre;Npy-GFP mice infected with the pCDH-CMV-FLEX-HA-S6K1-KR lentivirus. Body weight gain on chow (c) and RER in Agrp-DN-S6 and WT-DN-S6 mice. Data …
Figure 6
Leptin engages mTORC1 signaling in AGRP neurons to regulate thermogenesis.
Expression of p-mTORC1 (a, c) and colocalization of p-rpS6 and p-STAT3 (b, d) in Npy-GFP neurons following systemic leptin treatment. Leptin’s thermogenic effects in WT-CA-S6 and Agrp-CA-S6 (e), and …
Additional files
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Supplementary file 1
Real time PCR oligonucleotide sequences.
- https://doi.org/10.7554/eLife.22848.014
