Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF

Abstract

Obesity, high-fat diets, and subsequent type 2 diabetes (T2DM) are associated with cognitive impairment. Moreover, T2DM increases the risk of Alzheimer's disease (AD) and leads to abnormal elevation of brain beta-amyloid levels, one of the hallmarks of AD. The psychoactive alkaloid caffeine has been shown to have therapeutic potential in AD but the central impact of caffeine has not been well-studied in the context of a high-fat diet. Here we investigated the impact of caffeine administration on metabolism and cognitive performance, both in control rats and in rats placed on a high-fat diet. The effects of caffeine were significant: caffeine both (i) prevented the weight-gain associated with the high-fat diet and (ii) prevented cognitive impairment. Caffeine did not alter hippocampal metabolism or insulin signaling, likely because the high-fat-fed animals did not develop full-blown diabetes; however, caffeine did prevent or reverse a decrease in hippocampal brain-derived neurotrophic factor (BDNF) seen in high-fat-fed animals. These data confirm that caffeine may serve as a neuroprotective agent against cognitive impairment caused by obesity and/or a high-fat diet. Increased hippocampal BDNF following caffeine administration could explain, at least in part, the effects of caffeine on cognition and metabolism.

Figure 1

Compositions of high-fat diet (D12266B) and chow diet (D12489B).

Figure 2

Average group weights. Animals underwent surgery immediately following weighing in the 10^th week, and were tested after the week 11 weighing. Error bars = SEM. HFD animals gained significantly more weight, so that they were significantly heavier after 11 weeks on the diet [t(14) = 3.72, p<.05 vs chow-fed animals] whereas caffeine prevented this weight gain [t(14) = 2.92, p <.05 for comparison of high-fat and high-fat-caffeine groups]. HFD = high fat diet, HFDC = high fat diet plus caffeine, CD = control diet and CDC = control diet plus caffeine.

Figure 3

(A) Percent alternation performance. Error bars = SEM. (B) Mean arm entries during maze performance. Error bars = SEM. HFD animals had significantly worse alternation performance than either control animals or animals receiving both a high-fat diet and caffeine treatment, but there were no differences in number of arms entered.

Figure 4

A. Mean density ratio of hippocampal pAkt (Ser473) to total Akt. Ratios were normalised to beta-actin. B. Mean density ratio of plasma membrane GluT4 to total GluT4. (C & D) Representative blots for Akt and GluT4, respectively.

Figure 5

Mean hippocampal BDNF protein. Error bars = SEM