TABLE 3.
Summary of studies that investigated the role of orexin system in food intake and metabolism.
| Experiment | Species | Effect on food intake | References | ||
| Acute ICV infusion of orexins | Orexin-A | Freely fed rats (Wistar and Sprague-Dawley) | Increased food intake during the light phase | Sakurai et al., 1998; Edwards et al., 1999; Sweet et al., 1999; Dube et al., 2000; Jain et al., 2000; Yamanaka et al., 2000; Lopez et al., 2002 | |
| Freely fed rats (Wistar and Sprague-Dawley) |
Increased food intake during the early light phase (first 4-h post-infusion) Failed to stimulate feeding when given prior the onset of darkness Increased feeding when given 6h into the dark phase |
Haynes et al., 1999 | |||
| Freely fasted (18 h) rats (Wistar and Sprague-Dawley) | Increased food intake during the first 4-h post-infusion and reduced during the next 20-h | ||||
| Orexin-B | Freely fed rats (Wistar and Sprague-Dawley) | Increased food intake during the light phase |
Sakurai et al., 1998; Edwards et al., 1999; Jain et al., 2000 | ||
| Failed to stimulate feeding during the early light phase | Haynes et al., 1999 | ||||
| Chronic ICV infusion of orexins | Orexin-A | Freely fed rats (Wistar and Sprague-Dawley) |
Increased food intake during the light phase Decreased food intake during the dark phase | Haynes et al., 1999 | |
| orexin-B | Failed to stimulate feeding during the early light phase | ||||
| Microinjection of orexins | PVN | Orexin-A | Rats (Sprague-Dawley) | Increased food intake |
Dube et al., 1999 |
| DMN | |||||
| LH | Orexin-A | Rats (Sprague-Dawley) | Increased food intake |
Dube et al., 1999; Sweet et al., 1999; Thorpe et al., 2003 | |
| PFH | Orexin-A | Rats (Sprague-Dawley) | Increased food intake |
Dube et al., 1999; Sweet et al., 1999 | |
| ARC | Orexin-A | Rats (Sprague-Dawley) | Failed to stimulate feeding |
Dube et al., 1999 | |
| VMN | |||||
| POA | |||||
| CeA | |||||
| NTS | |||||
| VLPO | Orexin-A | Rats (Sprague-Dawley) | Failed to stimulate feeding Increased spontaneous physical activity Increased non-exercise activity thermogenesis Stimulate body weight loss |
Mavanji et al., 2015; Coborn et al., 2017 | |
| PVN | Orexin-B | Rats (Sprague-Dawley) | Failed to stimulate feeding | Dube et al., 1999; Sweet et al., 1999 | |
| DMN | |||||
| LH | |||||
| PFH | |||||
| ARC | |||||
| VMN | |||||
| POA | |||||
| CeA | |||||
| Pharmacological blockade of OX-Rs | OX1R antagonist (intraperitoneal administration) |
Freely fed rats (Sprague-Dawley and Lister hooded) | SB-334867-A given during the light phase decreased orexin-A-induced feeding | Haynes et al., 2000; Rodgers et al., 2001 | |
| Freely fasted (18 h) rats (Sprague-Dawley) | SB-334867-A given during the light phase reduced food intake during the first 4-h after overnight fasting | ||||
| Freely fed rats (Sprague-Dawley) | SB-334867-A given during early dark phase reduced food intake during the next 24-h post-injection SB-334867-A given for 3 days during early dark phase reduced food intake over 24-h on days one and three |
||||
| Freely fed rats (Osborne-Mendel and S5B/PI) | SB-334867-A given during early dark phase reduced food intake in both strain fed at high-fat diet but only in Osborne-Mendel fed at low-fat diet SB-334867-A given early dark phase decreased body weight only in the Osborne-Mendel but not in the S5B/PI |
White et al., 2005 | |||
| OX2R antagonist (in VLPO) | Freely fed rats (Sprague-Dawley) | JNJ-10397049 given during early light phase reduced spontaneous physical activity | Mavanji et al., 2015 | ||
| OX1R and OX2R antagonist (in VLPO) | Freely fed rats (Sprague-Dawley) | TCS-1102 (selective dual orexin receptors antagonist) given during early light phase decreased the effect of orexin-A on spontaneous physical activity and energy expenditure | Coborn et al., 2017 | ||
| Orexin neurons ablation | Transgenic mice (orexin/ataxin-3) | Decreased in food intake Decreased in water intake Decreased in locomotor activity Decreased energy expenditure Mice showed late-onset obesity Increased in the leptin level in females |
Hara et al., 2001; Hara et al., 2005; Fujiki et al., 2006; Zhang et al., 2007 | ||
| Transgenic mice (orexin-Cre) selective ablation of orexin neurons using diphtheria toxin fragment A |
Decreased food intake Decreased water intake Increased body weight Decreased blood glucose level No change in locomotion |
Inutsuka et al., 2014 | |||
| Orexin gene knockout | Transgenic mice (prepro-orexin knockout mice with C57/BL6J background) | Male mice showed a mild tendency to late-onset obesity | Hara et al., 2005 | ||
| Transgenic mice (prepro-orexin knockout mice with mixed genetic background C57/BL6J and 129SvEv) | Female mice showed more prominent late-onset obesity Increased in the leptin level in females |
Fujiki et al., 2006 | |||
| Chemoactivation of orexin neurons | Transgenic mice (orexin-Cre) |
Increased food intake Increased water intake Increased locomotor activity Increased the respiratory exchange ratio Increased blood glucose independently from food intake |
Inutsuka et al., 2014 | ||
| Transgenic mice (orexin-Cre) |
Increased spontaneous physical activity No change in food intake No change in water intake Increased energy expenditure especially in mice fed at high-fat diet |
Zink et al., 2018 | |||