Lipid Metabolism and Diabetes: In Sync with the Internal Circadian Clock

Depending on the timing of food intake, plasma lipid profiles change and affect insulin sensitivity. This is shown in a study by a research group led by PD Dr. Olga Ramich of DIfE and DZD, which has now been published in the 'Journal of Clinical Endocrinology & Metabolism'.

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Numerous physiological processes such as wakefulness and sleep, body temperature and blood pressure follow a regular 24-hour day / night rhythm. This rhythmicity of the internal circadian clock is controlled by a network of proteins and genes and can be influenced by light and meals. Disruptions of this sensitive system, for example due to jet lag or shift work, can promote overweight, insulin resistance and altered plasma lipid profiles and increase the risk of metabolic diseases such as type 2 diabetes.

Not only what and how, but also when
The team led by PD Dr. Olga Ramich, head of the research group “Molecular Nutritional Medicine“ at the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), investigates the relationships between the internal circadian  clock, meal composition and metabolic diseases. Ramich wanted to know exactly how the timing of a high carbohydrate meal compared to a high-fat meal would affect lipid metabolism and glycemic control. The research group analyzed the lipidome – that is, the set of all lipids in the plasma –  in 29 non-obese, healthy men.
 "Our results show very clearly that both meal composition and the timing of the meals during the day affect the plasma lipid profiles. For a third of all lipids, postprandial changes were dependent on whether the same meal was eaten in the morning or afternoon," said Ramich. Along with the plasma lipid profiles, insulin sensitivity also changed over the course of the day. "It is possible that the lipid patterns caused by the time of day may be the reason why our body reacts more sensitively to insulin in the morning than in the evening," the researcher explained.

Study design
The study consisted of two four-week dietary intervention phases. In one phase, the study participants ate a high-carb meal in the morning and a high-fat meal in the afternoon and evening. During the other phase, there was an early high-fat meal and a late high-carbohydrate meal. At the end of each respective phase, an investigation day followed, during which the participants came to the outpatient study center at DIfE and consumed two meals – one at 9:00 am and the other at 3:40 pm. As per previous dietary intervention phase, these test meals were either high carb or high fat. The research team examined the lipids in the plasma and the genes in the adipose tissue of the participants before and after each test meal. 

Dynamic analysis via high throughput shotgun plasma lipidomics
The scientists analyzed a total of 672 lipids from 14 lipid classes in the plasma of the study participants. They used the new high-throughput shotgun plasma lipidomics method. This represents a premiere, because no research group until now has used this method for the analysis of lipid metabolism in a dietary intervention study with humans. “For us, such dynamic analyses of the human lipidome are a milestone. For the first time, we can now see exactly how the plasma lipid profiles change during the day and under the influence of different meals," said Ramich. In order to understand the mechanisms by which plasma lipids are regulated, the scientists also investigated the expression of lipid metabolism genes in adipose tissue.

Recommendations for meal timing?
The study provides new insights into the circadian mechanisms of human lipid metabolism regulation and its relation to glycemic control. "It's easy to imagine that knowing the right time of day for certain meals will also be incorporated into future nutritional strategies for the prevention of type 2 diabetes," said Ramich. However, further studies are needed to understand the intricate mechanisms of how the internal circadian clock interacts with lipid metabolism and thus possibly decreases insulin sensitivity.

Original publication:
Kessler, K., Gerl, M. J., Hornemann, S., Damm, M., Klose, C., Petzke, K. J.,  Kemper, M., Weber, D., Rudovich, N., Grune, T., Simons, K., Kramer, A., Pfeiffer, A. F. H., Pivovarova-Ramich, O.: Shotgun lipidomics discovered diurnal regulation of lipid metabolism linked to insulin sensitivity in non-diabetic men. J Clin Endocrinol Metab., dgz176 (2019)

Background Information:

Financial support
The study was supported by grants from the German Research Foundation (DFG), the German Diabetes Association (DDG) and the German Center for Diabetes Research (DZD).