A workshop on ‘Dietary Sweetness—Is It an Issue?’

This report summarises a workshop convened by ILSI Europe on 3 and 4 April 2017 to discuss the issue of dietary sweetness. The objectives were to understand the roles of sweetness in the diet, establish whether exposure to sweetness affects diet quality and energy intake, and consider whether sweetness per se affects health. Although there may be evidence for tracking of intake of some sweet components of the diet through childhood, evidence for tracking of whole diet sweetness, or through other stages of maturity are lacking. The evidence to date does not support adverse effects of sweetness on diet quality or energy intake, except where sweet food choices increase intake of free sugars. There is some evidence for improvements in diet quality and reduced energy intake where sweetness without calories replaces sweetness with calories. There is a need to understand the physiological and metabolic relevance of sweet taste receptors on the tongue, in the gut and elsewhere in the body, as well as possible differentiation in the effects of sustained consumption of individual sweeteners. Despite a plethora of studies, there is no consistent evidence for an association of sweetness sensitivity/preference with obesity or type 2 diabetes. A multifaceted integrated approach, characterising nutritive and sensory aspects of the whole diet or dietary patterns, may be more valuable in providing contextual insight. The outcomes of the workshop could be used as a scientific basis to inform the expert community and create more useful dialogue among health care professionals

Health effects of erythritol

Erythritol (1,2,3,4-butanetetrol) is a non-caloric c4 polyol made by fermentation that has a sweetness 60–70% that of sucrose. The safety of erythritol has been consistently demonstrated in animal and human studies. Erythritol has a higher digestive tolerance compared to all other polyols because about 90% of the ingested erythritol is readily absorbed and excreted unchanged in urine. Erythritol is used in a wide range of applications for sweetening and other functionalities, e.g., in beverages, chewing gum and candies. In this review, we summarise the health effects of erythritol described in the literature. We focus on studies involving the anti-cariogenic and endothelial protective effects of erythritol. We conclude that erythritol could be of great importance and could be considered to be the preferred sugar substitute for a rapidly growing population of people with diabetes or pre-diabetes to reduce their risk of developing diabetic complications

Nondigestible Carbohydrates Affect Metabolic Health and Gut Microbiota in Overweight Adults after Weight Loss

Background The composition of diets consumed following weight loss (WL) can have a significant impact on satiety and metabolic health. Objective This study was designed to test the effects of including a nondigestible carbohydrate to achieve weight maintenance (WM) following a period of WL. Methods Nineteen volunteers [11 females and 8 males, aged 20–62 y; BMI (kg/m2): 27–42] consumed a 3-d maintenance diet (15%:30%:55%), followed by a 21-d WL diet (WL; 30%:30%:40%), followed by 2 randomized 10-d WM diets (20%:30%:50% of energy from protein:fat:carbohydrate) containing either resistant starch type 3 (RS-WM; 22 or 26 g/d for females and males, respectively) or no RS (C-WM) in a within-subject crossover design without washout periods. The primary outcome, WM after WL, was analyzed by body weight. Secondary outcomes of fecal microbiota composition and microbial metabolite concentrations and gut hormones were analyzed in fecal samples and blood plasma, respectively. All outcomes were assessed at the end of each dietary period. Results Body weight was similar after the RS-WM and C-WM diets (90.7 and 90.8 kg, respectively), with no difference in subjectively rated appetite. During the WL diet period plasma ghrelin increased by 36% (P < 0.001), glucose-dependent insulinotropic polypeptide (GIP) decreased by 33% (P < 0.001), and insulin decreased by 46% (P < 0.001), but no significant differences were observed during the RS-WM and C-WM diet periods. Fasting blood glucose was lower after the RS-WM diet (5.59 ± 0.31 mmol/L) than after the C-WM diet [5.75 ± 0.49 mmol/L; P = 0.015; standard error of the difference between the means (SED): 0.09]. Dietary treatments influenced the fecal microbiota composition (R2 = 0.054, P = 0.031) but not diversity. Conclusions The metabolic benefits, for overweight adults, from WL were maintained through a subsequent WM diet with higher total carbohydrate intake. Inclusion of resistant starch in the WM diet altered gut microbiota composition positively and resulted in lower fasting glucose compared with the control, with no apparent change in appetite. This trial was registered at clinicaltrials.gov as NCT01724411

SH2-containing inositol phosphatase (SHIP-1) transiently translocates to raft domains and modulates CD16-mediated cytotoxicity in human NK cells

Membrane recruitment of the SH2-containing 5' inositol phosphatase 1 (SHIP-1) is responsible for the inhibitory signals that modulate phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways. Herb we have investigated the molecular mechanisms underlying SHIP-1 activation and its role in CD16-mediated cytotoxicity. We initially demonstrated that a substantial fraction of. SHIP-1-mediated 5' inositol phosphatase activity associates with CD16 zeta chain after receptor cross-linking. Moreover, CD16 stimulation on human primary natural killer (NK) cells induces the rapid and transient translocation of SHIP-1 in the lipid-enriched plasma membrane microdomains, termed rafts, where it associates with tyrosine-phosphorylated zeta chain and shc adaptor protein. As evaluated by confocal microscopy, CD16 engagement by reverse antibody-dependent cellular cytotoxicity (ADCC) rapidly induces SHIP-1 redistribution toward the area of NK cell with target cells and its codistribution with aggregated rafts where CD16 receptor also colocalizes. The functional role of SHIP-1 in the modulation of CD16-induced cytotoxicity was explored in NK cells infected with recombinant vaccinia viruses encoding wild-type or catalytic domain-deleted mutant SHIP-1. We found a significant SHIP-1-mediated decrease of CD16-induced cytotoxicity that is strictly dependent on its catalytic activity. These data demonstrate that CD16 engagement on NK cells induces membrane targeting and activation of SHIP 1, which acts as negative regulator of ADCC function

PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway

Although membrane phospholipid phosphatidylinositol-4,5bisphosphate (PIP2) plays a key role as signaling intermediate and coordinator of actin dynamics and vesicle trafficking, it remains completely unknown its involvement in the activation of cytolytic machinery. By live confocal imaging of primary human natural killer (NK) cells expressing the chimeric protein GFP-PH, we observed, during effector-target cell interaction, the consumption of a preexisting PIP2 pool, which is critically required for the activation of cytolytic machinery. We identified type I phosphatidylinositol-4-phosphate5-kinase (PI5KI) alpha and gamma isoforms as the enzymes responsible for PIP2 synthesis in NK cells. By hRNA-driven gene silencing, we observed that both enzymes are required for the proper activation of NK cytotoxicity and for inositol-1,4,5-trisphosphate (IP3) generation on receptor stimulation. In an attempt to elucidate the specific step controlled by PI5KIs, we found that lytic granule secretion but not polarization resulted in impaired PI5KI alpha and PI5KI gamma-silenced cells. Our findings delineate a novel mechanism implicating PI5KI alpha and PI5KI gamma isoforms in the synthesis of PIP2 pools critically required for IP3-dependent Ca2+ response and lytic granule release