Intermittent energy restriction (IER) has become the subject of considerable scientific interest as a potential dietary approach for weight-loss and improving cardiometabolic health. This approach involves intermittent periods of total or partial energy restriction (ER) alternated with non-restricted intake, and has been studied in rodent and human populations.This review aims to provide an overview of the IER literature to date, with a specific focus on its effects on cardiometabolic health indices in rodents and humans.Current evidence from studies in rodents and humans suggests that IER is capable of promoting weight-loss and/or favourably influencing an array of cardiometabolic health indices, with equal or greater efficacy than conventional continuous ER approaches. Putative mechanisms include the effects of IER on adipose tissue physiology, stress resistance and fat distribution within visceral and intra-hepatic sites. However, a large proportion of this mechanistic evidence is limited to indirect observations and/or has come from rodent studies requiring translation into humans. Furthermore, whilst there is some indication that total IER and the array of partial IER protocols which have been developed may elicit distinct biological effects, our knowledge around this is limited as only a small number of rodent studies have directly addressed this.Ultimately, whilst much remains to be learned about IER, including its mechanisms of action and long-term efficacy, the positive findings to date serve to highlight promising avenues for future research.

Purpose of reviewGlucose-dependent insulinotropic polypeptide (GIP) plays an important role in the enteroinsular axis, stimulating insulin secretion. In addition, it has extrapancreatic actions, which may have pathophysiological relevance. This review highlights recent findings with regard to GIP's actions both within the enteroinsular axis and beyond it, and discusses evidence for the therapeutic potential of GIP receptor agonists and antagonists for the treatment of type 2 diabetes mellitus and possibly obesity. Recent findings GIP signalling pathways have been investigated using transgenic animal models, either lacking or overexpressing a defective GIP receptor. The dependence of early-phase insulin potentiation by GIP on K ATP channel activity, and of late-phase insulin secretion on other signals, has been demonstrated. GIP receptor agonists and antagonists resistant to enzymatic degradation and with a greater potency than native GIP have recently been developed. Their activity in animal studies suggests a novel and effective treatment of type 2 diabetes. Extrapancreatic actions of GIP have received little recent attention, with notable exceptions being the investigation of aberrant GIP receptor expression in Cushing's disease, and a possible role for GIP in vascular endothelial function. SummaryThe role of GIP in stimulating insulin secretion continues to be a primary focus for research, and the availability of various GIP-receptor knockout mice have helped to elucidate GIP's signalling pathways. A range of GIP receptor agonists and antagonists show promise in the treatment of type 2 diabetes, but as yet no clinical studies have been undertaken. Studies implicating GIP beyond the enteroinsular axis remain few and often negative, with the exception of effects on the vascular endothelium and the adrenal gland.