Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 1 • January 2013


Timed High Fat Diet Resets Circadian Metabolism and Prevents Obesity

We reported in the October 2012 issue of this newsletter on a very recent study1 in mice that found that when the mice were restricted to eating only at night, they could eat as much as they wanted of a high fat diet and not become obese, whereas mice that could eat whenever they wanted (day and night) of the same diet would become obese. Most interestingly, the mice eating only at night ate the SAME AMOUNT OF FOOD as the mice that ate day and night, yet those eating only at night did not become obese whereas those eating at any time did become obese. Note that humans and mice have opposite circadian rhythms for activity. Humans are normally inactive at night and mice are normally inactive during the day.

By an odd coincidence, a similar paper was published in the FASEB J2 about a month later, but the second paper didn’t seem to be aware of the first paper’s publication and didn’t cite it. In fact, the authors of the second paper thought that their paper was the first to be published on the subject of time restricted feeding of a high fat diet. “Although nocturnal mice fed an HF [high fat] diet during the whole of the light phase gained significantly more weight than mice fed during the dark period [cites given: shown as 3 & 4 below] an HF [high fat] diet has never been tested for its effect under RF [restricted feeding].”2

The differences between the papers were interesting, however. The first paper reported on the effects of feeding mice a high fat diet restricted to eating only at night (during the normal active period for mice) as compared to mice eating a high fat diet ad lib (any time of the day or night). The results showed a significantly higher weight gain in the mice eating the high fat diet day and night as compared to the mice eating the same diet but only at night. The photographs in the paper showing a typical example of a mouse that ate only at night and a typical example of a mouse that ate at any time of the day or night were very impressive, with the mouse eating only at night having an obviously leaner appearance as compared to the fat looking mouse that ate at any time.

The second paper, however, fed their RF (restricted feeding) mice for 18 weeks for 4 hours a day (from 4 to 8 hours after lights on (in other words, during the light period of the day), rather than (as in the first paper) during the dark period of the day. The researchers2 state that “[w]e have recently shown that long-term daytime RF can increase the amplitude of clock gene expression, increase expression of catabolic factors, and reduce the levels of disease markers, leading to better health.” The also note that “[m]any physiological activities normally dictated by the SCN [suprachiasmatic nucleus, location of the endogenous circadian clock] are altered by daytime RF.”

The implication is that RF, restricted feeding, can produce beneficial effects whether the feeding is restricted to night or to day. Interestingly, it has been found that animals exposed less than about 8 hours a day to a potentially addictive drug do not develop addiction. Since chronic overeating involves similar physiological pathways as drug addiction2b it may be that it is the period of restriction that is important in the weight gain-limiting effects of food restriction, not the part of the day that the eating is restricted to.

The researchers2 also included a group of mice that ate the RF (restricted diet) but with an LF (low fat) content. They measured several markers of metabolic activity and adiposity (fatness) in the four groups of mice, RF-HF, RF-LF, and AL-HF (ad lib high fat diet), and AL-LF (ad lib low fat diet). Results included, for example, that the AL groups had higher levels of the adiposity hormone leptin as compared with the RF groups. Leptin levels were 2-fold higher in the RF-HF group as compared to the RF-LF group, a marker of increased satiety in the RF-HF group. The daily levels of TNF-alpha, a major proinflammatory cytokine, were ~10% up-regulated in the AL-HF group, whereas the RF-HF group had levels similar to those of the AL-LF group, which indicates less inflammation on the high fat diet when fed for a restricted time.

The restricted time-fed high fat diet group had reduced cholesterol levels and the development of insulin resistance was prevented or delayed as compared to the AL-HF diet. Moreover, the researchers found that the shifts induced in circadian clock genes by a high fat diet can be rectified by timed feeding.

The authors conclude that “[o]ur results show that the timed HF diet leads to a unique metabolic phenotype of calorie intake equal to that of AL-HF mice but with reduced body weight. The total activity of RF-HF mice was higher than that of AL-HF and lower than that of RF-LF mice, correlating with their body weight.” They suggest that timed meals on a high fat diet may be easier to achieve than attempting to avoid high fat diets, since the latter are so much more palatable than low fat diets.

References

1. Hatori et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high fat diet. Cell Metab 15:848-60 (2012).

2. Sherman et al. Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB J 26:3493-502 (2012).

2b. Johnson & Kenny. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci 13(5):635-41 (2010).

3. Arble et al. Circadian timing of food intake contributes to weight gain. Obesity 17:2100-2 (2009).

4. Salgado-Delgado et al. Food intake during the normal activity phase prevents obesity and circadian desynchrony in a rat model of night work. Endocrinol 151:1019-29 (2010).

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