KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

A Healthier Beverage Choice is Based on a Subjective Assessment of Sweet Taste

Despite promising interventions to lower people’s daily sugar consumption, such as health- or taste-focused labels, the consumption of sugar-sweetened beverages (SSBs) continues to rise. To improve the effectiveness of existing labels, the way people process sugar amounts in grams (g) as displayed on beverages seems to merit elucidation. For example, do people perceive the difference in the amount of sugar, and thus in the subjective sweet taste, between two beverages according to Weber’s law? Additionally, is that perceived difference the cause of their beverage choice? In order to investigate these questions, participants in this online experiment first had to estimate the sugar difference between two beverages based on grams and then decide whether they would switch to a lower-sugar beverage. We found that participants’ different estimates followed Weber’s law. The choice of the lower-sugar beverage, however, depended on how large they personally perceived that difference. In other words, the choice was independent of the ratio. These results show that future labels, rather than indicating the total amount of sugar, should indicate whether the reduction, for example in the amount of sugar compared to another beverage, was perceived as significant by others.

KLF10 integrates circadian timing and sugar signaling to coordinate hepatic metabolism

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

The Moderating Role of Response to a Blood Glucose Challenge in Postprandial Cognition Following Consumption of Milk, Fruit Juice, and Water (FS05-05-19)

Objectives Results from recent studies indicate that milk facilitates cognition in children and college students with higher fasting glucose, particularly compared to a beverage higher in sugar (i.e., fruit juice). Although other findings suggest that low-sugar options facilitate cognition in persons with larger glycemic responses to meal or glucose challenges, studies thus far have artificially dichotomized glycemic response measures, a practice that introduces imprecision and decreases statistical power. The present investigation examined postprandial cognition following milk, apple juice, and water among adults, with response to a high-sugar beverage challenge considered as a moderator. We hypothesized that participants who showed a larger glycemic response to a high-sugar beverage (apple juice) would perform better following a low-sugar beverage (2% milk) compared to juice. Methods Forty-four healthy adults attended three morning sessions after fasting overnight. In a randomized, counterbalanced, crossover design, participants completed baseline cognitive testing (CNS Vital Signs), followed by ingestion of 8 oz of 2% milk, apple juice, or water. Postprandial cognitive testing occurred 30, 90, and 150 min post-ingestion. Plasma glucose was measured pre-consumption, as well as 30, 60, 90, 120, 150, and 180 minutes after each beverage, with glycemic response assessed as the incremental area under the curve (iAUC) for plasma glucose. Processing Speed and Executive Function domain scores were analyzed using linear mixed modeling. Results After adjusting for age and BMI, analyses showed significant Beverage*iAUC*Time interactions comparing water and milk for both Processing Speed (b = 1.11 * 10–4, P = 0.01) and Executive Function (b = 7.00 * 10–6, P = 0.03). For both composites, persons with larger glycemic responses performed better after drinking milk versus water at 30 minutes, while this pattern reversed at 150 minutes. No significant differences were observed overall between apple juice and the other beverage conditions. Conclusions Milk consumption may acutely (∼30–60 min) facilitate cognitive performance in persons with a larger glycemic response to a high-sugar beverage challenge. However, this pattern appears to reverse as blood glucose returns toward pre-consumption values. Funding Sources Work funded by the National Dairy Council.

Intragastric gelation of mixed soy protein isolate and alginate as well as its effect on postprandial glucose response and satiety

The goal of the study is to investigate the effect of alginate on sucrose release and in vitro gastric digestion of soy protein isolate (SPI) in model beverages as well as to determine whether consumption of the model beverages would affect postprandial blood glucose response and appetite in healthy adults. Model beverages containing 5% w/v SPI, 0 to 0.20% w/v alginate and 10% w/v sucrose were prepared by heating the mixtures at 85 áµ’C for 30 min at pH 6.0 or 7.0. Characterizations of beverages included determination of zeta-potential, particle size analysis and rheological properties measurement. Digestion patterns and sucrose release were determined after 0 to 2 h in-vitro gastric digestion using SDS-PAGE and HPLC analysis, respectively. Results showed that increasing alginate concentration led to increased zeta-potential value, particle size as well as increased viscosity and pseudoplastic behavior; however, no phase separation was observed in any of the samples. In the absence of alginate, the SPI beverage could form a weak intragastric gel only at a pH of 6.0 after mixing with simulated gastric fluid (SGF), while at pH 7.0 a gel was formed only in the presence of alginate. Formation of the intragastric gel led to delayed protein digestion and slower release of sucrose. Higher resistance to digestion and a slower sucrose release rate were exhibited at increased alginate concentration, and to alesser extent, at pH 6.0. This suggests that electrostatic interaction between SPI and alginate that occurred when the beverages were under gastric condition could be responsible for the intragastric gelation. The hypothesis that beverages showing intragastric gel formation in the in vitro study could be translated into in vivo applications was tested in a clinical trial. In the clinical trial, after an overnight fast, twelve healthy subjects were asked to consume six standardized breakfast beverages in a randomized order: a 122 kcal sugar beverage (CONT), a 122 kcal sugar beverage with alginate (ALG), a 172 kcal sugar beverage with SPI at pH 7 (SPI-7) or pH 6 (SPI-6), a 172 kcal sugar beverage with mixed SPI and alginate at a pH 7 (SPI+ALG-7) or pH 6 (SPI+ALG-6). Subjects consumed one of the beverages at time 0. Blood samples were drawn at -15, 0, 15, 30, 45, 60, 90 and 120 min and questionnaires were completed immediately following the blood draw at each time point. Results showed that, compared to CONT, consumption of SPI-6, SPI+ALG-7 and SPI+ALG-6 significantly lowered peak blood glucose concentration and 1-h incremental area under the curve (AUC). SPI+ALG-6 also exhibited a significant reduction in 2-h AUC. No significant effect on appetite was found in any condition. Interactions between the protein and alginate during digestion and formation of an intragastric gel could play an important role in influencing postprandial blood glucose response. In conclusion, we demonstrated the possible formation of an intragastric gel resulted from the SPI and alginate mixture under certain conditions, which subsequently delayed protein digestion and sucrose release from the matrix. Compared with CONT, consumption of beverages that formed an intragastric gel (SPI+ALG-7 and SPI+ALG-6) attenuated the postprandial glycemic concentration in healthy adult subjects. These results could potentially lead to the formulation of SPI beverage with functionality to lower postprandial glycemic response.