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Mitochondrial impairment following neonatal overfeeding: A comparison between normal and ischemic-reperfused hearts
Cristiane de Moura Freitas1, Luciana Caroline Paulino do Nascimento1, Glauber Rudá Feitoza Braz2
1Laboratory of Biochemistry and Exercise Biochemistry, Biochemistry and Physiology Graduate Program, CAV-Federal University of Pernambuco, Recife, Pernambuco, Brazil.
Insights
Neonatal overfeeding severely impacts cardiac mitochondria, causing impairments similar to ischemia-reperfusion injury. This early-life nutritional insult increases long-term cardiovascular disease risk.
Area of Science:
- Cardiovascular Science
- Mitochondrial Biology
- Nutritional Science
Background:
- Overweight and obesity are linked to cardiovascular diseases, with mitochondria playing a key role in cardiac metabolism.
- Obesity can originate in early postnatal life, suggesting critical developmental periods for metabolic programming.
- Mitochondrial dysfunction is a significant factor in the pathophysiology of cardiovascular impairments.
Purpose of the Study:
- To investigate the effects of neonatal overfeeding on cardiac mitochondrial bioenergetics and oxidative balance in rats.
- To assess the impact of ischemia-reperfusion (I/R) insult on overfed rats.
- To compare the detrimental effects of neonatal overfeeding and I/R insult on cardiac mitochondria.
Main Methods:
- Wistar rat litters were divided into control and overfed groups during lactation.
- Male offspring were fed standard chow ad libitum until sacrifice at 30 and 60 days.
- Cardiac mitochondrial bioenergetics and oxidative balance were evaluated, with some animals subjected to I/R insult.
Main Results:
- Neonatal overfeeding significantly affected cardiac mitochondrial bioenergetics and oxidative balance at both ages.
- Overfed rats showed resilience to additional I/R insult, suggesting prior mitochondrial deregulation.
- Overfeeding disengaged electrical mitochondrial coupling and potentiated oxidative stress, mimicking I/R effects.
Conclusions:
- Neonatal overfeeding deregulates cardiac mitochondria, comparable in detrimental effect to ischemia-reperfusion insult.
- Early-life nutritional insults program mitochondria for impairments, increasing cardiovascular disease risk.
- Neonatal overfeeding exacerbates oxidative stress and mitochondrial dysfunction throughout life.
Abstract:
Overweight and obesity are established factors underpin several metabolic impairments, including the cardiovascular. Although the diversity of factors involved in overweight/obesity-induced cardiovascular diseases, mitochondria has been highlighted due to its role in cardiac metabolism. As obesity can be originated in early postnatal life, the current study evaluates the effects of neonatal overfeeding on the cardiac mitochondrial bioenergetics and oxidative balance in rats that underwent an ischemia-reperfusion insult. Seventy-two hours after delivery, Wistar rat litters were randomly assigned into the control (C; nine pups per mother) and the Overfed (OF; three pups per mother) groups throughout the lactation period. At weaning, male offspring were fed with laboratory chow ad libitum until sacrifice at 30 and 60 days of life. Mitochondrial heart bioenergetics and oxidative balance showed to be deeply affected by neonatal overfeeding at both ages. Interestingly, after ischemia-reperfusion insult I/R (Langendorff or mineral oil incubation), most parameters evaluated in OF animals were not influenced by additional ischemic-reperfusion injury. Our findings demonstrated that suckling overfeeding deregulates cardiac mitochondrial alike to ischemia-reperfusion insult by disengaging electrical mitochondrial coupling and potentiate oxidative stress, wherein the neonatal overfeeding shows to be so detrimental as I/R. Our findings support the concept that nutritional insults in the critical development periods increase the risk for cardiovascular disease and mitochondria impairments throughout life while oxidative damage change between molecular targets.
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