Expression of UCP2 in Wistar rats varies according to age and the severity of obesity

Abstract

Obesity, a complex metabolic disorder, is characterized by mitochondrial dysfunction and oxidative stress. Increased expression of uncoupling protein 2 (UCP2) during obesity is an adaptive response to suppress the production of reactive oxygen species. The aims of this study were to compare the expression of UCP2 in diet-induced obese Wistar rats that differed according to age and their severity of obesity, and to compare UCP2 expression in the liver and muscle of these rats. UCP2 messenger RNA and protein expression was increased 4.6-fold (p < 0.0001) and 3.0-fold (p < 0.05), respectively, in the liver of the older and heavier rats. In contrast, UCP2 expression was decreased twofold (p < 0.005) in the muscle of these rats, while UCP3 messenger RNA (mRNA) was increased twofold (p < 0.01). Peroxisome proliferator-activated receptor alpha (PPARα) was similarly increased (3.0-fold, p < 0.05) in the liver of the older and more severe obese rats. Total protein content was increased (2.3-fold, p < 0.0001), while 5' adenosine monophosphate-activated protein kinase (AMPK) activity was decreased (1.3-fold, p = 0.05) in the liver of the older, heavier rats. No difference in total protein content and AMPK expression was observed in the muscle of these rats. This study showed that the expression of UCP2 varies according to age and the severity of obesity and supports the widely held notion that increased UCP2 expression is an adaptive response to increased fatty acid β-oxidation and reactive oxygen species production that occurs during obesity. An understanding of metabolic adaptation is imperative to gain insight into the underlying causes of disease, thus facilitating intervention strategies to combat disease progression.

Arabinoxylan activates lipid catabolism and alleviates liver damage in rats induced by high‐fat diet

“…The UCP2, as a mitochondrial inner membrane protein, was considered to accelerate fatty acid β‐oxidation and minimise reactive oxygen species production by uncoupling respiration from oxidative phosphorylation . Adipose differentiation‐related protein (ADRP) is reported to promote intracellular storage of neutral lipids (TG), and the gene expression level of ADRP is positively associated with the levels of intracellular lipid found in liver steatosis of rats fed high‐diet fat with PPARγ activation, agreement with the result in the present study.…”

“…Due to the imbalance between energy intake and expenditure, high‐fat diet could cause disorders of lipid metabolism, including a significant change of triglycerides (TG) and total cholesterol (TC) levels in blood and liver . Compared to other internal organs, the liver was thought to easily accumulate fat, resulting in mitochondrial dysfunction, oxidative stress and other damage . According to previous studies by Cho et al .…”

Mitochondrial inefficiency in infants born to overweight African-American mothers

“…( 31 , 32 ) Thus, increased UCP2 expression is considered an adaptive response to attenuate mitochondrial ROS production and protect against oxidative damage. ( 33 , 34 ) Evidence suggests that metabolic diseases, such as obesity or diabetes, are associated with elevated ROS levels and therefore elevated oxidative stress. ( 35 , 36 ) Data also show that increased ROS production, specifically superoxide radicals, activate UCP2 expression.…”

Uncoupling protein 2 and metabolic diseases

“…Nevertheless, the superoxide-UCP2 pathway is involved in pathogenesis of hyperglycemia, hyperlipidemia and β-cell dysfunction [10]. Several physiological states and pathological conditions (like high-fat diet, stress, exercise, obesity, and diabetes) are known to regulate UCP2 expression and activity [37–39]. Hence, substantial efforts are being made to understand how UCP2 is regulated.…”