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| Related pathology | Model | Treatment | Key effect(s) and mechanism(s) | Reference |
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| Stroke | Male apoE−/− mice (12–14 weeks) | Ad-APN (i.v.) 14 days prior to measurements | Effects: Ad-APN treatment reduced atherosclerotic lesion size, reduced the diameter of lipid droplets, and reduced VCAM-1 mRNA | Okamoto [66] |
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| Stroke | Male AdipoKO, eNOS KO, and WT mice (10–12 weeks) | Ad-APN (i.v.) 5 days prior to ischemia (1 hour of middle cerebral artery occlusion followed by 23 hours of reperfusion) | Effects: larger infarct size in AdipoKO mice compared to WT; reduced infarct size in AdipoKO and WT mice when pretreated with Ad-APN | Nishimura [69] |
| Mechanism: adiponectin reduces infarct size through eNOS; there was no alteration in infarct size in eNOS KO mice pretreated with Ad-APN |
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| Stroke | Male CD-1 mice (young: 3 months; age: 22–24 months) | AAV-APN (striatal injection) 7 days prior to transient middle cerebral artery occlusion | Effects: AAV-APN treatment improved motor function (neurological score, beam walk test, rotarod test, and corner test) and increased angiogenesis in young and aged mice | Miao [68] |
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| Alzheimer’s disease | SH-SY5YswAPP cell line | Adiponectin (10 μg/ml) for 2 h followed by hydrogen peroxide (200–800 μM) | Effect: improved neuronal survival with adiponectin incubation prior to insult | Chan [115] |
| Mechanisms: adiponectin is neuroprotective against oxidative stress via AdipoR1, AdipoR2, and APPL1; improved neuronal survival was prevented by knockdown of AdipoR1, AdipoR2, or APPL1 |
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| Alzheimer’s disease | Male C57BL/6J mice (8–14 weeks) | Osmotin (15 mg/kg, i.p.) at 3 or 40 days following administration of Aβ1–42 ( i.c.v.) | Effects: osmotin treatment improved Y-maze spontaneous alternations performance, reduced Aβ1–42 accumulation, and reduced tau hyperphosphorylation | Ali [118] |
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| Alzheimer’s disease | Male AdipoKO and WT mice (9 and 18 months) | | Effects: AdipoKO mice had impaired performance on MWM and increased expression of Aβ1–42, hyperphosphorylated tau, and pIRS-1S616 at 18 months | Ng [103] |
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| Alzheimer’s disease | SH-SY5YswAPP cell line | Adiponectin (10 μg/ml, trimeric) | Effects: adiponectin reduced Aβ1–42 expression and increased insulin sensitivity | Ng [103] |
| Mechanisms: adiponectin reduces Aβ1–42 through AdipoR1 and increases insulin sensitivity through AdipoR1 and AMPK; effects blocked by knockdown of AdipoR1 or inhibition of AMPK |
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| Alzheimer’s disease | Male APP/PS1 mice (5–12 months) | Osmotin (12 mg/kg/day i.p.) for 2 days or osmotin (5 mg/kg/day, i.p.) twice a week for 2–4 weeks | Effects: osmotin treatment increased NMDAR expression, improved hippocampal CA1 LTP, and improved performance on MWM | Shah [119] |
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| Alzheimer’s disease | SH-SY5YswAPP cell line | Osmotin (0.2 μM) for 24 hours | Effects: osmotin reduced expression of Aβ and increased expression of AMPK and SIRT1 | Shah [119] |
| Mechanism: osmotin alters expression of these proteins via AdipoR1; knockdown of AdipoR1 prevented these effects |
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| Alzheimer’s disease | Male C57BL/6J mice (5–11 weeks) | AdipoR1 knockdown (shRNA, i.v., weekly injection) | Effects: AdipoR1 knockdown mice displayed impaired performance on MWM, increased body weight, increased Aβ, and reduced pAMPKT172 | Kim [104] |
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| Depression | Male Adipo+/− and WT mice (9–12 weeks) | Globular (0.3 μg, i.c.v.) or full length (1 μg, i.c.v.) adiponectin | Effects: adiponectin deficient mice displayed increased susceptibility to depressive behaviors (social interaction, sucrose preference test, and learned helplessness following a social defeat paradigm); globular or full length adiponectin had antidepressant effect in WT mice (forced swim test) | Liu [132] |
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| Depression | Male AdipoKO and WT mice (8-9 weeks) | | Effects: running enhanced hippocampal neurogenesis and increased hippocampal adiponectin in WT but not AdipoKO mice | Yau [26] |
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| Depression | Neuro2a cell line | Trimeric adiponectin (3 μg/ml) | Effect: adiponectin incubation promoted cell proliferation | Yau [26] |
| Mechanism: adiponectin promotes cell proliferation through AdipoR1 in the Neuro2a cell line; siRNA knockdown of AdipoR1 but not AdipoR2 abolished adiponectin induced proliferation |
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| Anxiety | Male AdipoKO and WT mice (9 and 18 months) | | Effect: increased anxiety behavior in 9- and 18-month AdipoKO mice (open-field test) | Ng [103] |
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| PTSD | Male AdipoKO, AdipoR1 conditional KO, AdipoR2 KO, and WT mice (8–2 weeks) | Adiponectin (0.25 μg, intra-DG infusion) daily 3 days prior to fear extinction and 30 min prior to each extinction session | Effects: AdipoKO and AdipoR2 KO mice, but not AdipoR1 conditional KO mice, displayed slower contextual fear extinction learning; adiponectin infusion to DG of hippocampus facilitated extinction learning in WT mice | Zhang [27] |
| Mechanism: adiponectin facilitations extinction learning via AdipoR2; adiponectin infusion failed to facilitate extinction learning in AdipoR2 KO mice |
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| Misc. | Primary hippocampal neurons from Sprague-Dawley rats | Adiponectin (5 or 20 μg/ml) for 48 h followed by kainic acid (100 μM) for 12 h | Effects: adiponectin incubation improved neuronal survival, reduced expression of reactive oxygen species, and reduced caspase-3 activity | Qiu [114] |
| Mechanism: adiponectin promotes neuronal survival through AMPK; adiponectin enhancement of survival was prevented by an AMPK inhibitor |
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| Misc. | Primary neuronal stem cells from ICR mice | Adiponectin (30 μg/ml) for 4 days prior to high glucose (120 mM) | Effects: adiponectin incubation enhanced neurogenesis, increased AdipoR1 expression, and increased TLX expression | Song [28] |
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