. 2021 Nov 4;179(4):600–624. doi: 10.1111/bph.15682

TABLE 1.

The effect of activating or inhibiting GLP‐1 and GLP‐1 receptor expressing neurons in the brain on energy balance and glucose metabolism

Genetic marker	Acute effect	Signalling mechanism	Body weight	Lean mass	Fat mass	Food intake	EE	RER	Ambulatory activity	Blood glucose levels	ITT	Insulin sensitivity	GTT	PTT/hepatic glucose production/uptake	Taste aversion	References
Gcg‐Cre (NTS) (JAX #000664 x BAC RP23‐242F22)																Gaykema et al., ²⁰¹⁷
Chow ‐ Harlan 7912	Activation	AAV2/5‐hSyn‐DIO‐hM3Dq; UNC viral core	↔	N/A	N/A	↓ Chow; ↓ fast‐refeed	↓	↔	↓	Elevated (fed state)	↔	↔	↔	Improved PTT/no change glucose uptake	↔
DIO ‐ HCD: Research Diets D12331; DIO: Teklad TD.88137	Activation	AAV2/5‐hSyn‐DIO‐hM3Dq; UNC viral core	↓ after 5mo. DIO	↔	↓	↓ Daytime HCD sated; ↓ fast‐refeed HFD; ↓ fast‐refeed DIO	N/A	N/A	N/A	↔ (fed state)	N/A	N/A	N/A	↔	N/A
Gcg‐Cre (fibres in PVH) (mice from Gaykema et al., ²⁰¹⁷ )	Activation	AAV‐EF1a‐DIO‐ChR2; Addgene#: 20298	N/A	N/A	N/A	↓	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Liu et al., ²⁰¹⁷
	Inhibition	AAV‐EF1a‐DIO‐eArch3.0; N/A	N/A	N/A	N/A	↑	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Liu et al., ²⁰¹⁷
Gcg‐cre (NTS, DMV) (mice from Gcg‐Cre cryo‐preserved embryos ID 358‐UNC) ‐ standard chow	Activation	AAV8‐hSyn‐DIO‐hM3Dq	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Reduced (fasted state)	N/A	Improved	Improved	Reduced glucose production (3.5 hr post CNO)	N/A	Shi et al., ²⁰¹⁷
Ppg‐Cre (Gcg‐Cre ‐ mice from Gaykema et al., ²⁰¹⁷ )																Cheng et al., ²⁰²⁰
Chow ‐ Purina Lab Diet, 5001	Activation	AAV‐FLEX‐hM3Dq	↓ (multi‐day tx)	N/A	N/A	↓ Overnight fast‐refeed; ↓ @ start dark cycle	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
DIO ‐ HCD: Research Diets D12331; DIO: Teklad TD.88137	activation	AAV‐FLEX‐hM3Dq	N/A	N/A	N/A	↓ @ Start dark cycle	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
N/A	Inhibition	AAV‐hM4Di	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	↔	N/A	N/A
Ppg‐Cre [mice from GLU‐Cre12 ‐ Parker et al., ²⁰¹² ] ‐ standard chow	Activation	AAV2/8‐FLEX‐hM3Dq; B. Roth	↔	N/A	N/A	↓ @ 1, 2, & 4 hr after dark onset & first 24 hr	N/A	N/A	N/A	N/A	N/A	N/A	↔	N/A	N/A	Holt et al., ²⁰¹⁹
	Inhibition	AAV2‐FLEX‐hM4Di; B. Roth	N/A	N/A	N/A	↔ After dark onset; ↑ @ 1 hr 18 hr fast‐refeed	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Holt et al., ²⁰¹⁹
GLP‐1 receptor‐ires‐Cre (JAX #029283)	Activation	AAV8‐hSyn‐DIO‐hM3Dq; Addgene#: 44361	N/A	N/A	N/A	↓ @ 0.5–3 hr dark onset & 16 hr fast‐refeed	↔	↔	↔	N/A	N/A	N/A	N/A	N/A	N/A	Li, Navarrete, et al, ²⁰¹⁹
GLP‐1 receptor‐ires‐Cre (JAX #029283)	Inhibition	AAV8‐hSyn‐DIO‐hM4Di; Addgene#: 44362	N/A	N/A	N/A	↑ @ 0.5–3 hr light cycle	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	Li, Navarrete, et al, ²⁰¹⁹
Glp1r‐ires‐Cre/AAV‐GCaMP6s (calcium reporter)																Li, Navarrete, et al., ²⁰¹⁹
Chow (Teklad F6 Rodent Diet 8664)	N/A	AAV1‐CAG‐FLEX‐GCaMP6s	N/A	N/A	N/A	↑ fluorescence to food Presentation ‐ after fast refeed	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A
HFD (Research Diets D12492i)	N/A	AAV1‐CAG‐FLEX‐GCaMP6s	N/A	N/A	N/A	↑ Fluorescence to food presentation ‐ after fast refeed	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A	N/A

Note: ↑/↓ statistically significant response; Δ/∇ non‐significant trend; ↔ equivalent to control/ wild type.

Abbreviations: DIO, diet‐induced obese mice; DMV, dorsal motor nucleus of the vagus; EE, energy expenditure, HFD/HCD, high fat/high caloric diet; PVN, paraventricular hypothalamic nucleus; RER, respiratory exchange ratio.