Arcuate nucleus and lateral hypothalamic CART neurons in the mouse brain exert opposing effects on energy expenditure
- Garvan Institute of Medical Research, Australia
- Medical University of Graz, Austria
- Medical University Innsbruck, Austria
Figures
Figure 1
Validation of the expression sites of Cre-dependent AAV-hM3Dq-mCherry for CNO-mediated neuronal activation.
Fluorescence micrographs of coronal brain sections from respective Arc→hM3Dq (A) and LHA→hM3Dq (B) Cartptcre/+ mice, showing the mCherry reporter being specifically expressed in the respective …
Figure 2 with 1 supplement
CNO-mediated activation of hM3Dq-containing Arc CART neurons leads to a reduction in energy expenditure and physical activity in Cartptcre/+ mice.
Indirect calorimetric assessments following saline or CNO injection for the 24 hr time course of energy expenditure, VO2 and VCO2 (A, B), physical activity (C, D), and respiratory exchange ratio (E, …
Figure 2—figure supplement 1
CNO does not exert any effects on physical activity, energy expenditure and respiratory exchange ratio in the absence of hM3Dq-expression in Cartptcre/cre, Cartptcre/+and wild type mice.
Indirect calorimetric assessments following saline or CNO injection for the 24 hr time course of energy expenditure (A, B, C), physical activity represented as total count (D, E, F), and respiratory …
Figure 3
CNO-mediated activation of hM3Dq-containing Arc CART neurons leads to a decrease in body skin temperature in Cartptcre/+ mice.
Temperatures of the interscapular brown adipose tissue (BAT) and the lumbar back region, as well as the temperature differences between the inter-scapular and lumbar areas 2 hr following saline or …
Figure 4
CNO-induced activation of hM3Dq-positive CART neurons in the Arc increases 24 hr food intake and results in weight gain in homozygous Cartptcre/cre mice.
Food intake during fed state 24 hr following saline or CNO injection in Arc→hM3Dq mice, expressed both as absolute amounts of food intake (A, C) and as a percentage of body weight (B, D), for Cartptc…
Figure 5
CNO-mediated activation of hM3Dq-containing LHA CART neurons increases energy expenditure and physical activity in Cartptcre/+ mice.
Indirect calorimetric assessments following saline or CNO injection for the 24 hr time course of energy expenditure, VO2 and VCO2 (A, B), physical activity (C, D), and respiratory exchange ratio (E, …
Figure 6
CNO-mediated unilateral activation of hM3Dq-containing LHA CART neurons does not affect body temperature of Cartptcre/cre and Cartptcre/+ mice.
Temperatures of the BAT and the lumbar back region, as well as the temperature differences between the inter-scapular and lumbar areas of Cartptcre/cre (A) and Cartptcre/+ (B) mice measured by …
Figure 7
CNO-induced activation of hM3Dq-positive CART neurons in the LHA increases 24 hr food intake and body weight gain in heterozygous Cartptcre/+ mice.
Food intake during fed state 24 hr following saline or CNO injection in LHAhM3Dq mice, expressed both as absolute amounts (A, C) and as a percentage of body weight (B, D) for Cartptcre/cre and Cartpt…
Figure 8
CNO-mediated bilateral activation of hM3Dq-containing LHA CART neurons leads to elevation in physical activity, energy expenditure and respiratory exchange ratio in Cartptcre/+ mice.
Indirect calorimetric assessments following saline or CNO injection for the 24 hr time course of energy expenditure, VO2 and VCO2 (A, B), physical activity represented as total count (C, D), and …
Figure 9 with 1 supplement
CNO-mediated bilateral activation of hM3Dq-containing LHA CART neurons leads to increased body skin temperature in Cartptcre/cre and Cartptcre/+ mice.
Temperatures of the interscapular brown adipose tissue (BAT) (A, B), the lumbar back (D,E), the tail (G,H) and differences between BAT and lumbar temperatures (J, K) measured by high-sensitivity …
Figure 9—figure supplement 1
CNO does not exert any effects on body skin temperature in the absence of hM3Dq-expression in Cartptcre/cre, Cartptcre/+ and wild type mice.
Temperatures of the interscapular brown adipose tissue (BAT) (A, B, C), the lumbar back (D, E, F), the tail (G, H, I) measured by high-sensitivity infrared imaging 1, 3 and 6 hr after i.p. injection …
Figure 10 with 1 supplement
CNO-induced bilateral activation of hM3Dq-positive CART neurons in the LHA leads to an increase in ingestive behavior and body weight in heterozygous Cartptcre/+mice.
Cumulative food intake during fed state 6 hr following saline or CNO injection in bilateral LHA→hM3Dq Cartptcre/cre and Cartptcre/+ mice (A, B) as well as interaction with the food hopper (C, D). …
Figure 10—figure supplement 1
CNO does not exert any effects on ingestive behavior and body weight in the absence of hM3Dq-expression in Cartptcre/cre, Cartptcre/+ and wild type mice.
Cumulative food intake and food hopper interaction during fed state 6 hr following saline or CNO injection Cartptcre/cre (A, D) and Cartptcre/+ mice (B, E) without hM3Dq-injection and wild type mice …
Figure 11
hM3Dq-mCherry-positive CART neurons co-express GAD67 and MCH, but not orexin.
Fluorescence micrographs of coronal brain sections from respective LHA→hM3Dq Cartptcre/+ mice, showing partial co-expression of the mCherry reporter with GAD67 (A), and MCH (B) (white arrows, right …
Figure 12
CART neurons in the LHA are highly heterogeneous and co-localise with various neurotransmitters involved in energy homeostasis.
Representative fluorescence micrograph showing fluorescent CART neurons in the LHA of a CART-TRAP mouse (A). Enrichment (>1) or derichment (<1) of various neurotransmitter transcripts in the …
Additional files
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Supplementary file 1
Sequences of oligonucleotide primers used in qPCR
- https://doi.org/10.7554/eLife.36494.018
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Transparent reporting form
- https://doi.org/10.7554/eLife.36494.019
