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

TABLE 3.

Pharmacological effects of GLP‐1 receptor agonist and antagonists

Agonists Drug Body weight Food intake Fat mass GTT References
Genetic marker
Control/wild type GLP‐1, liraglutide, exendin‐4 Scrocchi et al., 1996; Sisley et al., 2014; Adams et al., 2018;
Standard chow ↓ ↓ N/A Improved Burmeister et al., 2017; Ghosal et al., 2017; Secher et al., 2014;
HFD ↓ ↓ ↓ Improved Kanoski et al., 2011; Alhadeff et al., 2012; Richard et al., 2014
Glp1r −/− GLP‐1 Scrocchi et al., 1996
Standard chow N/A ↔ N/A ↔
HFD N/A N/A N/A N/A
Nestin‐Cre (JAX #3771); GLP‐1 receptor lox/lox liraglutide Sisley et al., 2014
Chow (Harlan Teklad no. 7012) N/A ↓ @ 4 hr; ↔ @ 24 hr N/A Improved
HFD (D12331) ∇ ∇ @ 7 days & 14 days ∇ (14 days) Improved
Phox2b‐Cre (JAX #016223); GLP‐1 receptor lox/lox liraglutide Sisley et al., 2014
Chow (Harlan Teklad no. 7012) N/A ↓ @ 4 hr & 24 hr N/A Improved
HFD (D12331) ↓ ↓ @ 7 days & 14 days ↓ Improved
Vgat‐iCre, GLP‐1 receptor lox/lox liraglutide Adams et al., 2018
Standard chow
Male ↓ ↓ N/A N/A
Female ↓ ↓ N/A N/A
HFD (D12451); male only ↓ During 14 days treatment ↓ N/A N/A
Vglut‐iCre, GLP‐1 receptor lox/lox liraglutide Adams et al., 2018
Standard chow
Male No change @ 24 hr ↓ (Partial block) N/A N/A
Female No change @ 24 hr ↓ (Partial block) N/A N/A
HFD (D12451); male only ∇ During 14 days treatment ∇ N/A N/A
Nkx2.1‐Cre (JAX #8661); GLP‐1 receptor lox/lox exendin‐4 & liraglutide (peripheral dose) Burmeister et al., 2017
Chow (Harlan Teklad #2016) ↓ @ 1–10 days; ∇ 11–14 days ↓ N/A Improved
HFD (D12492) ↓ @ 1–14 days; sig less effect from control ↓ N/A N/A
Sim1‐Cre (JAX #6395); GLP‐1 receptor lox/lox exendin‐4 & liraglutide (peripheral dose) Burmeister et al., 2017; Ghosal et al., 2017
Chow (Harlan Teklad #2016); Harlan (3.1 kcal/g; ∼5% fat) N/A ↓ N/A Improved
HFD (D12492); Research Diets (4.54 kcal/g; ~40% fat) N/A ↓ N/A Improved
POMC‐Cre (JAX #5965); GLP‐1 receptor lox/lox exendin‐4 (peripheral dose) Burmeister et al., 2017
Chow (Harlan Teklad #2016) N/A ↓ N/A Improved
HFD (D12492) N/A ↓ N/A Improved
PVH lesion liraglutide Secher et al., 2014
Chow (no. 1324, Altromin, Brogaarden) ↓ N/A N/A N/A
HFD N/A N/A N/A N/A
SDA exendin‐4 & liraglutide Kanoski et al., 2011; Secher et al., 2014
Standard chow ↓ @ 1–14 days ↓ (Lira 6 hr); ↓ (lira & ex‐4 24 hr) N/A N/A
High fat diet N/A N/A N/A N/A
lPBN injection; YFP‐PPG exendin‐4 Richard et al., 2014
Standard chow ↓ ↓ N/A N/A
HFD N/A N/A N/A N/A
VTA injection; wild type exendin‐4 Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 ↓ (24 hr) ↓ @ 1 hr (sucrose); ↓ @ 24 hr (chow) N/A N/A
HFD (D12492) N/A ↔ (1 and 3 hr); ↓ (6 and 24 hr) N/A N/A
NAc core injection; wild type exendin‐4 N/A N/A Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 ↓ ↓ (Sucrose ); ↑ (chow) N/A N/A
HFD (D12492) N/A ↔ (1 hr); ↓ (3, 6, and 24 hr) N/A N/A
NAc shell injection; wild type exendin‐4 Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 ↓ ↔ (Sucrose); Δ @ 3 hr (chow) N/A N/A
HFD (D12492) N/A ↔ (1 and 3 hr); ↓ (6 +24 hr) N/A N/A
Control/ wild type Burmeister et al., 2017; Alhadeff et al., 2012; Richard et al., 2014; Sandoval et al., 2008
Standard/rodent chow exendin‐9 & des‐His1,Glu8‐exendin‐4 (dH‐EX) ↑ ↑ N/A Impaired
HFD N/A N/A N/A N/A N/A
I.C.V. injection Sandoval et al., 2008
Standard/rodent chow des‐His1,Glu8‐exendin‐4 (dH‐EX) N/A N/A N/A Impaired
HFD N/A N/A N/A N/A N/A
Nkx2.1‐Cre (JAX #8661); GLP‐1 receptor lox/lox Burmeister et al., 2017
Chow (Harlan Teklad #2016) exendin‐9 N/A N/A N/A Impaired
HFD (D12492) N/A N/A N/A N/A N/A
Sim1‐Cre (JAX #6395); GLP‐1 receptor lox/lox Burmeister et al., 2017
Chow (Harlan Teklad #2016) exendin‐9 N/A N/A N/A Trend toward impairment
HFD (D12492) N/A N/A N/A N/A N/A
lPBN injection; YFP‐PPG Richard et al., 2014 Alhadeff et al., 2014
Standard chow ‐ Purina Rodent Chow, 5001/standard chow exendin‐9 ↑ ↑ N/A N/A
HFD ‐ Research Diets: 45% kcal from fat exendin‐9 ↔ ↑ N/A N/A
VTA injection; wild type Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 N/A N/A N/A N/A N/A
HFD (D12492) exendin‐9 Δ ↑ (3 and 6 hr) N/A N/A
NAc core injection; wild type Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 N/A N/A N/A N/A N/A
HFD (D12492) exendin‐9 ↔ ↑ (1 and 3 hr) N/A N/A
NAc shell injection; wild type Alhadeff et al., 2012
Chow Purina Rodent Chow, 5001 N/A N/A N/A N/A N/A
HFD (D12492) exendin‐9 ↔ ↔ N/A N/A

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

Abbreviations: DIO, diet‐induced obese mice; EE, energy expenditure; HFD/HCD, high fat/high caloric diet.; IPBN, lateral parabrachial nucleus; NAc, nucleus accumbens; POMC, pro‐opiomelancortin; SDA, subdiaphragmatic vagal deafferentation; VTA ventromedial hypothalamus.