Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

Marjana Rahman Sarker,Nathalie Sumien,Michael Forster,Nopporn Thangthaeng,Frank Filipetto,Susan Franks,Claudia Miele

doi:10.1371/journal.pone.0140431

Marjana Rahman Sarker, Nathalie Sumien + Show 5 more

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https://doi.org/10.1371/journal.pone.0140431

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Abstract

Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

Highlights

Complementary and alternative therapies have significant potential to expand current treatment options for obese patients, especially those who can be classified as overweight and class 1 obese yet do not meet clinical criteria for appetite suppressant drugs or bariatric surgery [1]
The current study focused on the therapeutic potential of the polyphenol curcumin, which has gained an increased interest in recent years as a potential treatment for obesity-related comorbidities as well as neurodegenerative disorders [3,4,5]
A recent analysis of data on 7 strains of commonly used laboratory rodents suggested that beneficial effects of chronic caloric restriction on life-span were directly proportional to the degree of weight gained by midlife under the ad libitum (AL) feeding regimen [12]

Summary

Introduction

Complementary and alternative therapies have significant potential to expand current treatment options for obese patients, especially those who can be classified as overweight and class 1 obese yet do not meet clinical criteria for appetite suppressant drugs or bariatric surgery [1]. A recent analysis of data on 7 strains of commonly used laboratory rodents suggested that beneficial effects of chronic caloric restriction on life-span were directly proportional to the degree of weight gained by midlife under the AL feeding regimen [12] These results challenge the use of AL feeding as a control condition and, perhaps more importantly, suggest that under standard laboratory conditions, middle-aged AL fed mice are translational analogues of overweight and mildly obese humans [10]. The association of inflammation with poor cognition may be influenced by the reciprocal relationship inflammation shares with oxidative stress in several pathologies, which includes chronic obesity [26,27,28] Both IL-6 and TNF-α, whose levels are increased in several pathologies, have been reported to promote the production of reactive oxygen species, a process which reinforces activation of pro-inflammatory transcription factors. The hypothesis for this study was that dietary curcumin would promote weight loss and reduce adiposity, thereby improving cognition via a concurrent decrease in inflammation and oxidative stress

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