Reply to Erren et al. Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on “Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846”

We would like to thank Erren et al. [...]

Chronodisruption: Origin, Roots, and Developments of an 18-Year-Old Concept. Comment on Desmet et al. Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag. Nutrients 2021, 13, 3846

We read with interest the article by Desmet and colleagues entitled “Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag” [...]

Effects of Restricted Feeding on Growth Performance, Intestinal Immunity, and Skeletal Muscle Development in New Zealand Rabbits

This study aimed to explore the effects of different feeding restriction levels on the growth performance, intestinal immunity, and skeletal muscle development of meat rabbits. Additionally, we studied whether complete compensatory growth could be obtained post 2 weeks of restricted feeding, in order to seek a scientific mode of feeding restriction. Each of three groups was exposed to 3 weeks of feeding restriction and 2 weeks of compensatory growth. The 15% feeding restriction showed a negligible effect on the final body-weight of the rabbits (p > 0.05), but significantly reduced the feed-to-weight ratio (p < 0.05); reduced diarrhea and mortality; and increased digestive enzyme activity and antioxidant capacity. However, a 30% feeding-restriction level substantially reduced the growth rate of the rabbits (p < 0.05), impaired skeletal muscle development, and showed no compensatory growth after 2 weeks of nutritional recovery. Additionally, immunoglobulin and antioxidant enzyme synthesis were impaired due to reduced nutritional levels, and levels of pro-inflammatory factors were increased during the compensation period. The IGF1 mRNA expression decreased significantly (p < 0.05), whereas MSTN and FOXO1 expression increased noticeably (p < 0.05). Moreover, protein levels of p-Akt and p-p70 decreased significantly in the 15% feeding restriction group. Overall, the 15% feeding limit unaffected the weight and skeletal muscle development of rabbits, whereas the 30% feeding limit affected the growth and development of skeletal muscle in growing rabbits. The PI3K/Akt signaling pathway is plausibly a mediator of this process.

Weight Loss and High-Protein, High-Fiber Diet Consumption Impact Blood Metabolite Profiles, Body Composition, Voluntary Physical Activity, Fecal Microbiota, and Fecal Metabolites of Adult Dogs

Canine obesity is associated with reduced lifespan and metabolic dysfunction, but can be managed by dietary intervention. This study aimed to determine the effects of restricted feeding of a high-protein, high-fiber (HPHF) diet and weight loss on body composition, physical activity, blood metabolites, and fecal microbiota and metabolites of overweight dogs. Twelve spayed female dogs [age: 5.5±1.1 yr; body weight (BW): 14.8±2.0 kg, body condition score (BCS): 7.9±0.8] were fed a HPHF diet during a 4-wk baseline phase to maintain BW. After baseline (wk 0), dogs were first fed 80% of baseline intake and then adjusted to target 1.5% weekly weight loss for 24 wk. Body composition using dual-energy x-ray absorptiometry and blood samples (wk 0, 6, 12, 18, 24), voluntary physical activity (wk 0, 7, 15, 23), and fresh fecal samples for microbiota and metabolite analysis (wk 0, 4, 8, 12, 16, 20, 24) were measured over time. Microbiota data were analyzed using QIIME 2. All data were analyzed statistically over time using SAS 9.4. After 24 wk, dogs lost 31.2% of initial BW and had 1.43±0.73% weight loss per wk. BCS decreased (P&lt;0.0001) by 2.7 units, fat mass decreased (P&lt;0.0001) by 3.1 kg, and fat percentage decreased (P&lt;0.0001) by 3.1 kg and 11.7% with weight loss. Many serum metabolites and hormones were altered, with triglycerides, leptin, insulin, C-reactive protein, and interleukin-6 decreasing (P&lt;0.05) with weight loss. Relative abundances of fecal Bifidobacterium, Coriobacteriaceae UCG-002, undefined Muribaculaceae, Allobaculum, Eubacterium, Lachnospira, Negativivibacillus, Ruminococcus gauvreauii group, uncultured Erysipelotrichaceae, and Parasutterella increased (P&lt;0.05), whereas Prevotellaceae Ga6A1 group, Catenibacterium, Erysipelatoclostridium, Fusobacterium, Holdemanella, Lachnoclostridium, Lactobacillus, Megamonas, Peptoclostridium, Ruminococcus gnavus group, and Streptococcus decreased (P&lt;0.01) with weight loss. Despite the number of significant changes, a state of dysbiosis was not observed in overweight dogs. Fecal ammonia and secondary bile acids decreased, while fecal valerate increased with weight loss. Several correlations between gut microbial taxa and biological parameters were observed. Our results suggest that restricted feeding of a HPHF diet and weight loss promotes fat mass loss, minimizes lean mass loss, reduces inflammatory marker and triglyceride concentrations, and modulates fecal microbiota phylogeny and activity in overweight dogs.

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding

In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD+, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD+ also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime. Genetic uncoupling of nutrient state from NADH redox state through transduction of the water-forming NADH oxidase from Lactobacillus brevis (LbNOX) increases daytime body temperature and blood and liver acyl-carnitines. LbNOX expression in TRF-CR mice induces oxidative gene networks controlled by brain and muscle Arnt-like protein 1 (BMAL1) and peroxisome proliferator-activated receptor alpha (PPARα) and suppresses amino acid catabolic pathways. Enzymatic analyses reveal that NADH inhibits SIRT1 in vitro, corresponding with reduced deacetylation of SIRT1 substrates during TRF-CR in vivo. Remarkably, Sirt1 liver nullizygous animals subjected to TRF-CR display persistent hypothermia even when NADH is oxidized by LbNOX. Our findings reveal that the hepatic NADH cycle links nutrient state to whole-body energetics through the rhythmic regulation of SIRT1.