The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis. Type 2 diabetes, which is reaching epidemic proportions worldwide, is often associated with obesity and an imbalance in organismal lipid homeostasis. Therefore, understanding how insulin regulates lipid biosynthesis and breakdown is necessary. Surprisingly, the molecular mechanisms by which insulin regulates fatty acid catabolism are not entirely understood. We show here that insulin signaling regulates expression of acyl-CoA Synthetases (ACS). ACSs couple fatty acids to Coenzyme A, thereby activating them for subsequent biochemical reactions. In Drosophila, we find that insulin signaling modulates expression of one ACS called Pudgy, which activates fatty acids for beta-oxidation. Modulation of pudgy expression leads to changes in overall organismal lipid homeostasis. Likewise, we show that in mammalian cells insulin signaling regulates expression of a number of ACSs and that ACS expression modulates steady-state lipid levels.

Background: Increasing evidence highlights that accumulating sitting time in prolonged bouts is detrimental to cardiometabolic health. Objectives: This systematic review aimed to compare the effects of fractionating prolonged sitting with frequent short bouts of standing and light-intensity walking on cardiometabolic health markers and conduct a meta-analysis for differences in systolic blood pressure (SBP), postprandial glucose and insulin. Methods: Experimental randomised crossover trials with at least three intervention arms that assessed interrupting sitting with frequent short bouts of standing and light-intensity walking over a single day compared to a prolonged sitting condition were retrieved. These studies measured at minimum one marker of cardiometabolic health in adults > 18 years. An electronic search was completed on the 2nd of August 2021, searching PubMed and Web of Science Core Collection, Scopus, Embase, Cochrane Library and APA PsycINFO. Risk of bias was assessed using a modified Downs and Black checklist. A meta-analysis was conducted using calculated Cohen’s d quantifying the magnitude of difference between experimental conditions. Results: Seven studies met the inclusion criteria for the systematic review. All seven studies were included within the meta-analysis for postprandial glucose, four studies were pooled for postprandial insulin and three for SBP. Biomarkers of cardiometabolic health were discussed qualitatively if fewer than three studies measured and reported the variable. A meta-analysis of seven acute, 1-day randomised crossover trials that sampled mixed-sex adults (aged > 18 years) who were predominately overweight or participants with obesity found that standing as an interruption to prolonged sitting significantly reduced postprandial glucose (∆ = − 0.31, 95% CI − 0.60, − 0.03; z = − 2.15, p < 0.04) but had no significant effect on insulin or SBP. Light-intensity walking was shown to significantly attenuate postprandial glucose (∆ = − 0.72, 95% CI − 1.03, − 0.41; z = − 4.57, p < 0.001) and insulin (∆ = − 0.83, 95% CI − 1.18, − 0.48; z = − 4.66, p < 0.001) compared to continued sitting. When comparing light-intensity walking breaks compared to standing breaks a significant reduction in glucose (∆ = − 0.30, 95% CI − 0.52, − 0.08; z = -2.64, p < 0.009) and insulin (∆ = − 0.54, 95% CI − 0.75, − 0.33; z = -4.98, p < 0.001) was observed. Both standing and light-intensity walking showed no effect on SBP. Conclusions: Frequent short interruptions of standing significantly attenuated postprandial glucose compared to prolonged sitting; however, light-intensity walking was found to represent a superior physical activity break. The feasibility and longitudinal implications of breaking sedentary behaviour with light-intensity walking should be investigated in a free-living setting. Registration: Not available.

Whey protein (WP) is a widely consumed nutritional supplement, known to enhance strength and muscle mass during resistance training (RT) regimens. Muscle protein anabolism is acutely elevated following RT, which is further enhanced by WP. As a result, there is reason to suggest that WP supplementation may be an effective nutritional strategy for restoring the acute loss of contractile function that occurs following strenuous RT. This systematic review and meta-analysis provides a synthesis of the literature to date, investigating the effect of WP supplementation on the recovery of contractile function in young, healthy adults. Eight studies, containing 13 randomised control trials (RCTs) were included in this review and meta-analysis, from which individual standardised effect sizes (ESs) were calculated, and a temporal overall ES was determined using a random-effects model. Whilst only half of the individual studies reported beneficial effects for WP, the high-quality evidence taken from the 13 RCTs was meta-analysed, yielding overall positive small to medium effects for WP from < 24 to 96 h (ES range = 0.4 to 0.7), for the temporal restoration of contractile function compared to the control treatment. Whilst the effects for WP were shown to be consistent over time, these results are limited to 13 RCTs, principally supporting the requirement for further comprehensive research in this area.