Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 6 • October 2012

Remarkable New Finding on Weight Gain and WHEN You Eat:

Eating As Much As They Wanted But Only During the Active Part of the Day Protected Mice Against Obesity, High Insulin Levels, Fatty Liver, and Inflammation

A test of how body weight is regulated by the daily rhythms of internal clocks has been reported in a new study.1 Mice that were allowed to eat all that they wanted of a high fat diet but only during the normally active (dark) part of the day (FT—time restricted feeding mice on a high fat diet) were protected against excess weight gain despite eating the same amount of a high fat diet (HFD) as the mice (FA) fed the same diet but that could eat anytime (day or night) and became obese. These results, which are likely to be similar in people, suggest that you might be able to eat all you want and not get fat if you do not eat after dark when circadian rhythms alter how you metabolize food.

The researchers first fed the animals a high fat diet and found that not only did they develop obesity, diabetes, and metabolic syndrome (dysfunctions associated with diabetes, such as insulin resistance), but they exhibited dampened feeding and circadian rhythms.1 The next part of the studies involved feeding the animals the high fat diet but either restricted to the dark period of the day or not restricted. “The time-restricted high-fat-fed mice showed significantly increased thermogenesis and improved rhythms in nutrient utilization, leading to reduced adiposity and liver steatosis [fatty liver], normal glucose tolerance, reduced serum cholesterol, increased bile acid production, and improved motor function.”

Mice were also fed normal chow under either ad lib (eat any time) or time-restricted access to food during their natural nocturnal feeding time to establish the differences between eating at particular times. The mice fed normal chow ad lib showed a nocturnal increase in RER (respiratory exchange ratio) and food intake reflecting feeding followed by carbohydrate utilization, while RER and food intake declined during the day consistent with lipid oxidation during fasting.1 The mice fed a HFD ad lib had dampened diurnal rhythms in food intake and RER. On the other hand, the animals fed either normal chow or a HFD on a time-restricted (eating at night only) regimen had improved RER diurnal rhythms compared to their ad lib counterparts, with higher RER during feeding and reduced RER during fasting, indicative of increased glycolysis (use of glucose for deriving energy from oxidative metabolism) and fat oxidation (deriving energy from fat metabolism), respectively.1 Most amazingly, the HFD fed animals ate about the same amount of food, whether eating ad lib or only during the night, yet the animals eating only at night did not become obese while the ad lib mice did.

The researchers investigated the biochemical changes that were taking place in the mice during the eating during the night only as compared to the eating at any time. Eating a HFD ad lib normally perturbs the function of nutrient sensors and regulators, such as CREB, mTOR, and AMPK, resulting in an increase in tissue growth and metabolic dysfunctions associated with energy overload, such as insulin resistance, fat stored in inappropriate areas such as in muscle, etc. The nutrient sensors are supposed to be regulated by circadian rhythms entrained in part by normal exposure to food which, in wild mice, would be taking place at night and with a much lower fat content than a HFD experimental mouse food.

In the study,1 for example, the diurnal rhythm of food intake (normal chow) induced CREB phosphorylation (activation) during daytime fasting and increased pS6 (m-TOR stimulated during nighttime feeding). Importantly, “in FA [high fat diet ad lib fed] mice, the perturbed circadian feeding pattern blunted pCREB [phosphorylated CREB] and pS6 oscillations and led to constitutively elevated pCREB and reduced pS6 levels.”

In contrast, “in the FT [high fat diet eaten only at night] mice, the tRF imposed a diurnal rhythm in food intake, thereby restoring the daytime peak in pCREB and nightime peak in pS6.”

On page 850 of the paper1 is a startling photo of a representative FA (high fat diet ad lib fed) mouse alongside a representative FT (high fat diet fed but only at night) mouse showing how fat the FA mouse looks compared to the normal looking FT mouse. “These coordinated changes in gene expression and metabolites show that the tRF [time restricted feeding] regimen temporally reprograms glucose metabolism away from gluconeogenesis [glucose synthesis by the liver] toward glycolysis, reduced glutathione, and anabolic pathways. Accordingly, FT mice did not display the hallmarks associated with glucose intolerance found in diet-induced obesity, instead showing glucose tolerance and insulin levels comparable to the control NA [normal chow ad lib fed] mice. The overall improvement in metabolic state also paralleled improved motor coordination in the mice under tRF paradigms.”1

“Most of the extra body weight in the FA [high fat diet ad lib] mice was due to increased adiposity. FA mice showed 70% more fat deposits than those in the FT [high fat diet time restricted] mice … hyperleptinemia associated with diet-induced obesity in FA mice was absent in FT mice.”1

These results are interestingly correlated with the results we reported in an earlier newsletter of another study2 in which restricting food consumption to the active phase (dark) of the day prevented weight gain in mice, but that even low levels of light would disrupt the circadian timing of food intake, causing the mice exposed to dim light to eat more during the day, gain weight, and develop glucose intolerance. In that study, mice exposed to dim light ate 55.5% of their food during the light phase, as compared to 36.5% by mice in the standard light/dark cycle.

In an earlier study,3 scientists found that “an enzyme that responds to nutrient availability—AMPK (adenosine monophosphate-activated protein kinase)—directly phosphorylates the core clock protein cryptochrome 1 (CRY1), thereby marking it for degradation.” Thus, the interaction between the systems regulating circadian rhythms and feeding cycles is well established.

We have both changed our eating habits to eat most of our food during the day. The experimental results in mice are compelling, not only for the improvement in weight but for reduced oxidative stress and inflammation and even improved motor coordination—it is very likely to work similarly in people (except that in people, eating should take place mostly during the day rather than at night) and it is certainly a great deal easier (though not entirely without the need for some willpower) than a low calorie diet.


  1. Hatori et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet,” Cell Metabolism 15:848-60 (2012).
  2. Fonken et al. Light at night increases body mass by shifting the time of food intake. Proc Nat Acad Sci USA 107(43):18664-9 (2010).
  3. Suter and Schibler. Feeding the clock,” Science 326:378-9 (2009).

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