Impairment of mitochondrial beta-oxidation in rats under cold-hypoxic environment.
Mitochondrial beta-oxidation of fatty acid provides a major source of energy in mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient temperatures, causes alteration in metabolic homeostasis. Several studies have depicted that hypoxic exposure in small mammals causes hypothermia due to hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia tolerance in animals. The present study investigated the rate of beta-oxidation and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male Sprague Dawley rats (190-220 g) were randomly divided into eight groups (n = 6 rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7 days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, (14)C-palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in CH1 and CH7 as compared to respective controls. HAD activity was significantly reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed controls in muscle and liver, respectively. A concomitant decrease in (14)C-palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia and cold-hypoxia suggested hypometabolic state. It can be concluded that ss-oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment due to the persisting hypometabolic state in cold-hypoxia exposure.
Dutta
Arkadeb
A
Nutrition Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India. arka_07dutta@rediffmail.com
Vats
Praveen
P
Singh
Vijay K
VK
Sharma
Yogendra K
YK
Singh
Som N
SN
Singh
Shashi B
SB
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002247:Carbon Isotopes; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D003080:Cold Temperature / Q000009:adverse effects*; D000860:Hypoxia / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002247:Carbon Isotopes; D020738:Leptin; D010168:Palmitates; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002334:Carnitine O-Palmitoyltransferase