(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders.

The discovery of the endocannabinoidome (eCBome) is evolving gradually with yet to be elucidated functional lipid mediators and receptors. The diet modulates these bioactive lipids and the gut microbiome, both working in an entwined alliance. Mounting evidence suggests that, in different ways and with a certain specialisation, lipid signalling mediators such as N-acylethanolamines (NAEs), 2-monoacylglycerols (2-MAGs), and N-acyl-amino acids (NAAs), along with endocannabinoids (eCBs), can modulate physiological mechanisms underpinning appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition, and immunity. This knowledge has been primarily utilised in pharmacology and medicine to develop many drugs targeting the fine and specific molecular pathways orchestrating eCB and eCBome activity. Conversely, the contribution of dietary NAEs, 2-MAGs and eCBs to the biological functions of these molecules has been little studied. In this review, we discuss the importance of (Wh) olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N) utrition (WHEN), in the management of obesity and related disorders.

Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development.

In Drosophila larvae, growth and developmental timing are regulated by nutrition in a tightly coordinated fashion. The networks that couple these processes are far from understood. Here, we show that the intestine responds to nutrient availability by regulating production of a circulating lipoprotein-associated form of the signaling protein Hedgehog (Hh). Levels of circulating Hh tune the rates of growth and developmental timing in a coordinated fashion. Circulating Hh signals to the fat body to control larval growth. It regulates developmental timing by controlling ecdysteroid production in the prothoracic gland. Circulating Hh is especially important during starvation, when it is also required for mobilization of fat body triacylglycerol (TAG) stores. Thus, we demonstrate that Hh, previously known only for its local morphogenetic functions, also acts as a lipoprotein-associated endocrine hormone, coordinating the response of multiple tissues to nutrient availability.

Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila.

Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by Imp-L2 mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.

[Consumption of ultra-processed foods and relationship between nutrient intake and obesity among participants undergoing specific health checkups provided by National Health Insurance].

Objective　Obesity associated with an increased consumption of ultra-processed foods (UPF) has been reported by studies abroad using the NOVA food classification system, an international framework for classifying food according to the degree of processing. However, no such study has been conducted in Japan. In this study, we evaluated the association between UPF consumption, nutrient intake, and obesity using the NOVA system.Method　In September 2017, we conducted a survey using a questionnaire of patients who had attended routine health checkups in Manazuru Town, Kanagawa Prefecture and collected their three-day dietary records as well as medical examination results. The final analysis included 169 patients (66 men, 103 women). Food consumed by the respondents were classified into four groups of NOVA systems. The dietary share of UPF (UPF energy ratio) was compared to total energy intake (except alcoholic beverages and eating out). Nutrient intake and obesity risk were compared across the UPF energy ratio tertile (low, middle, and high intake). Covariance and logistic regression analysis were conducted and adjusted based on age, sex, household structure, education, income, and total energy intake (except energy-providing nutrients, macronutrients, and protein intake per body weight) to analyze the association between UPF consumption and nutrient intake. Finally, for obesity, we adjusted for physical activity and smoking status using a similar analysis of the relationship between UPF consumption and energy providing nutrients and macronutrients.Result　Approximately 75% of patients investigated were older than 65 years. The average (standard deviation) UPF energy ratio was 29.7% (15.0). There were no significant differences in socioeconomic status among groups according to the UPF energy ratio. The high-UPF group had a significantly greater total energy intake. However, the protein energy ratio, protein intake per body weight, dietary fiber, and vitamins A, E, K, B1, B6, C, niacin, folic acid, potassium, magnesium, and iron intake were significantly lower in the high-UPF group. Moreover, the high-UPF group had a significantly higher BMI. The odds ratio for obesity was higher (4.51[1.50-13.57]) in the high-UPF group than in the low-UPF group (1.00).Conclusion　Those who consumed more UPF had lower protein intake and suffered from multiple vitamin and mineral deficiencies. Furthermore, their energy intake was greater, and the odds ratio for obesity was significantly higher. It has been suggested that excessive UPF consumption warrants further attention.

Dietary patterns are associated with likelihood of hepatic steatosis among US adults.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease is a rapidly growing public health problem. In this study, we explored the association between dietary patterns (DPs) and fatty liver and liver function tests. METHODS: This was a cross-sectional study using data from the US community-based National Health and Nutrition Examination Survey. Participants with data on dietary intake, blood pressure, and status for diabetes mellitus were analyzed. DPs were determined by principal components analysis. Analysis of covariance and logistic regression models accounted for the survey design and sample weights. RESULTS: Of the 20 643 eligible participants, 45.7% had prevalent fatty liver. Three DPs collectively explained 50.8% of variance in dietary nutrients consumption. The first DP was representative of a diet containing high levels of saturated and mono-unsaturated fatty acids, total fat and carbohydrate; the second DP comprised vitamins, minerals and dietary fibre; and the third DP was mainly representative of polyunsaturated fatty acids. In adjusted multivariable regression models, participants in the top quarter of the second DP had 34% lower odds of prevalent fatty liver (odds ratio 0.66 [95% confidence interval [CI]: 0.43-0.71]), while those in the top quarter of the first DP had 86% higher odds (1.86 [95% CI: 1.42-2.95]) of prevalent fatty liver, relative to participants in the bottom quarter of each of the DPs. CONCLUSION: Our findings suggest that a diet with high load of vitamins, minerals, and fiber content is associated with a lower prevalence of non-alcoholic fatty liver disease.

Prognostic nutritional index and postoperative outcomes in patients with colon cancer after laparoscopic surgery.

PURPOSE: The prognostic nutritional index (PNI) is calculated using the serum albumin and peripheral lymphocyte counts. We sought to assess the correlation between the preoperative PNI and postoperative outcomes in patients with colon cancer treated with laparoscopic surgery. METHODS: We included 896 colon cancer patients who underwent curative laparoscopic colectomy between January 2013 and March 2016. To identify any predictors of the postoperative outcomes, we compared the clinical characteristics and immunonutritional parameters, including the PNI, between patients classified as the Clavien-Dindo grade 2 or higher (n = 99) with those classified as grade 0 or 1 (n = 797). RESULTS: A longer surgical time and a preoperative low PNI (< 49.8) (odds ratio; 1.913, p = 0.002) were independent predictors of postoperative complications according to a multivariate analysis. A preoperative low PNI was significantly associated with an older age, a lower performance status, a lower BMI, higher CEA levels, an advanced T status, lymph node metastasis, a longer operative time, a higher blood loss, a larger tumor size, treatment with a combined resection, a longer time to bowel recovery, a longer postoperative hospital stay, and a poor overall survival. CONCLUSIONS: A preoperative low PNI was found to be significantly associated with the incidence of postoperative complications, an advanced tumor status, and a poor prognosis. Further research is needed to understand how to best clinically utilize this promising parameter.

Prognostic nutrition index affects the prognosis of patients undergoing trimodality therapy for locally advanced non-small cell lung cancer.

PURPOSE: Trimodality therapy, comprised of induction chemoradiotherapy (iCRT) followed by surgery, is a highly invasive treatment option for locally advanced non-small cell lung cancers (LA-NSCLCs; defined as a heterogenous disease). We conducted this study to investigate the prognostic nutritional index (PNI) of LA-NSCLC patients undergoing trimodality therapy, which has not been studied in detail before. METHODS: The subjects of this retrospective study were 127 patients who underwent trimodality therapy between 1999 and 2016. We measured the PNI at three points: before iCRT (pre-iCRT), before the operation, and after the operation. RESULTS: PNIs decreased significantly as treatment progressed. Patients with clinical T3/4 (cT3/4) disease had a significantly lower PNI than those with cT1/2 disease, but the extent of lymph-node metastasis did not affect the PNI at any point. Using the cut-off values of receiver-operating curve analyses, multivariable analyses revealed that a high PNI pre-iCRT correlated significantly with a better survival of LA-NSCLC patients, especially those with cT3/4 disease (hazard ratio 3.84; 95% confidential interval 1.34-12.5, P = 0.012). CONCLUSIONS: Measuring the PNI before trimodality therapy is important for predicting the clinical outcome of patients with LA-NSCLC, with differing predictive ability according to the disease extent. Perioperative intensive nutritional intervention must be considered for patients who undergo trimodality therapy for LA-NSCLC.

Covid-19 and dietary socioecology: Risk minimisation.

Pandemics have shaped humanity over and over again, but the coronavirus outbreak of 2019-2020 is in a world at the tipping point of catastrophic climate change. Its origins and distinction derive from over-population with inequity and an industrial revolution since the 17th century which has exploited fossil fuels as a globalised energy source, a period now described as the anthropocene. Asymptotic ecosystem loss and dysfunction, for people whose being is socioecological, makes ultimate survival tenuous. Microbial forms of life jump species when habitats are destroyed, or their host misused. Our innate immunity depends on our general health and fitness- social, mental, physical, and nutritional, in step with nature and its rhythms through walking in it, enjoying sunlight and sleep. Biodiversity and the associated benefit of food variety, after being breast-fed, is the key descriptor of a healthful, sustainable, accessible, and acceptable way of eating. How this pattern might contribute to our resilience in the face of a highly transmissible and biologically evasive virus is becoming clear. It may also be possible to compliment usefully preventive vaccination and therapeutic healthcare and rehabilitation through a greater understanding of our nutritional biology.

Dietary Fibre for the Prevention of Cardiovascular Disease.

Cardiovascular disease (CVD) remains the major cause of mortality worldwide. The importance of diet in optimising cardiovascular health has been illustrated in various studies. The role of dietary fibre in CVD prevention remains debatable. Dietary fibre helps to reduce total cardiovascular risk by engendering better cholesterol level and blood pressure, for example. The observed benefits, particularly for CVD mortality, seem to correlate with the level of dietary fibre intake in a dose-response fashion. Total aversion to foods with carbohydrates could potentially restrict the sources of dietary fibre that are available, particularly whole grain products which are recommended in the Mediterranean diet and the Eat-Lancet report on healthy diets. Further high-quality nutrition research is required to discern the absolute benefits of dietary fibre for CVD prevention. This may have implications for total healthcare expenditure, by means of public health and prevention policy that would serve to reduce the global burden of CVD.

Handling the inpatient's hospital 'Career' - Are nurses laying the groundwork for healthy meal and nutritional care transitions?

This qualitative study examined hospital nurses' methods in handling meal and nutrition care during inpatient time, with an underlying focus on undernourished older adult. Observations and interviews were used to document nurses' methods through the span of a transition (defined by an entry, passage, and exit). The study finds inconsistencies in care methods due to institutional processes restricting both mealtime care and nutritional logging of information throughout hospitalization. It is concluded that the consequences of these inconsistencies must be recognized and that new approaches to meals and nutritional care should be introduced in order to provide greater flexibility. Based on the assumption that mobilizing patient resources is pivotal for meal and nutritional care, it is argued that it may be important to mobilize patient resources during mealtime and in nutritional logging of information in order to increase the visibility of meal and nutritional care in patient transitions within the institution and across settings. Both nurses' methods and institutions developmental initiatives regarding meal and nutritional care need to accommodate the differences between what in this paper is defined as social-bodily care and text-based care. This could be met through care methods that take place with, more than for the patient.

Different physiological roles of insulin receptors in mediating nutrient metabolism in zebrafish.

Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a ( insra) and b ( insrb) caused ß-cell hyperplasia and lethality from 5 to 16 days postfertilization (dpf) (Yang BY, Zhai G, Gong YL, Su JZ, Han D, Yin Z, Xie SQ. Sci Bull (Beijing) 62: 486-492, 2017). In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively. A high-carbohydrate diet was provided for insulin receptor knockout zebrafish from 60 to 120 dpf to investigate phenotype inducement and amplification. We observed hyperglycemia in both insra-/- fish and insrb-/- fish. Impaired growth hormone signaling, increased visceral adiposity, and fatty liver were detected in insrb-/- fish, which are phenotypes similar to the lipodystrophy observed in mammals. More importantly, significantly diminished protein levels of P-PPARα, P-STAT5, and IGF-1 were also observed in insrb-/- fish. In insra-/- fish, we observed increased protein content and decreased lipid content of the whole body. Taken together, although Insra and Insrb show overlapping roles in mediating glucose metabolism through the insulin-signaling pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis through activation of the growth hormone-signaling pathway, whereas Insra primarily acts to promote lipid synthesis via glucose utilization.

Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats.

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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.

Nutritional biomarkers: Current view and future perspectives.

There is a poor relationship between nutrient intake and existing nutritional biomarkers due to variety of factors affecting their sensitivity and specificity. To explore the impact of nutrients at molecular level and devising a sensitive biomarker, proteomics is a central technology with sirtuins as one of the most promising nutritional biomarker. Sirtuins (seven mammalian sirtuins reported so far) have been reported to perform protein deacetylases and ADP-ribosyltransferases activity. It is distributed in different cellular compartments thereby controlling several metabolic processes. Sirtuins are oxidized nicotinamide adenine dinucleotide dependent, which implicates a direct effect of the metabolic state of the cell on its activity. Calorie restriction upregulates the mammalian sirtuin protein levels in variety of tissues and organs where it acts upon both histone and nonhistone substrates. Sirtuin senses nutrient availability and impacts gluconeogenesis, glycolysis, and insulin sensitivity. It deacetylates and inhibits the nuclear receptor that activates fat synthesis and adipogenesis in the body, leading to fat loss and bringing favorable cellular and health changes. Sirtuins mediates intracellular response that promotes cell survival, DNA damage repair thereby increasing the cell longitivity. The activation of sirtuins brings a wide spectrum of other health benefits and its activity levels are indicative of nutritional status as well as disease progression in cancer, inflammation, obesity, cardiovascular diseases, and viral infections. There are several foods that activate sirtuin activity and offer significant health benefits by their consumption.

Partnering with families to promote nutrition in cancer care: feasibility and acceptability of the PIcNIC intervention.

BACKGROUND: Malnutrition is frequent in patients with cancer, particularly those in advanced stages of the disease. The aim of the present study was to test the feasibility of a family-centred nutritional intervention, based on the Family Systems theory and past research. METHODS: This was a single-arm trial assessing feasibility (eligibility, recruitment and retention rates); acceptability by patients, family caregivers and health professionals; intervention fidelity, and energy/protein intake (in one site only). Two sites were involved; one each in Australia (AUS) and Hong Kong (HK), with one site delivering the intervention to oncology patients receiving curative treatments in the hospital, and the other to advanced cancer patients in the home. RESULTS: The sample included 53 patients (23 from AUS and 30 from HK), 22 caregivers (3 from AUS and 19 from HK) and 30 health professionals (20 from AUS and 10 from HK). Recruitment was difficult in the acute inpatient oncology care setting (AUS) and feasibility criteria were not met. Sufficient recruitment took place in the home care setting with advanced cancer patients in HK. Patients, family members and health professionals found the intervention helpful and acceptable, and patients and families indicated they would take part in the future in a similar study. Energy and protein intake improved from baseline to end of intervention (mean 22 kcal/kg/day to 26 and 0.9 g/kg/day to 1.0 respectively). CONCLUSION: The new intervention is feasible in a home setting when delivered to patients with advanced cancer, acceptable to patients and families, and has the potential to improve nutritional status in patients. A large randomised trial is warranted in the future.

Feeding the microbiota: transducer of nutrient signals for the host.

Advances in microbiome science cast light on traditional concepts on nutritional science, and are poised for clinical translation. Epidemiologic observations which linked lifestyle factors to risk of disease are being re-interpreted with mechanistic insight based on improved understanding of the microbiota. Examples include the role of dietary fibre in disease prevention, the deleterious effects of highly restricted diets, and the contribution of the microbiota to over- and undernutrition. While the microbiota transduces nutrient signals for the host, food and habitual diet shape the composition of the gut microbiota at every stage of life. The composition and diversity of food intake determines which microbes will colonise, flourish, persist, or become extinct. Disruption of the developing microbiota in infancy contributes to the risk of immune and metabolic disease in later life, whereas loss of microbes in the elderly due to monotonous diets has been linked with unhealthy ageing and frailty. This should influence modern dietary advice regarding prevention and management of chronic non-communicable inflammatory and metabolic disorders, and will inform the design of infant and future food formula. The microbiota profile is also emerging as a biomarker to predict responsiveness to dietary interventions and promises to make personalised nutrition a reality.

Cellular and molecular responses of adult testis to changes in nutrition: novel insights from the sheep model.

This review explores the cellular and molecular mechanisms that regulate spermatogenesis in the post-pubertal testis that is regressing in response to mild undernutrition, using the sexually mature male sheep as a model. Testis regression leads to reductions in daily sperm production and in the quality of ejaculated spermatozoa (poorer movement, DNA damage). There is also a reduction in spermatogenic efficiency that appears to be caused, at least partially, by increases in germ cell apoptosis. Sertoli cell number does not change with testis regression, although about 1% of Sertoli cells do appear to retain proliferative ability after puberty. On the other hand, Sertoli cell function is disrupted during testis regression, as evidenced by a disorganization of tight junctions and indications that cell differentiation and maturation are reversed. Disrupted Sertoli cell function can explain, at least partially, the increase in germ cell apoptosis and any decrease in the rate of spermatogenesis, the two major contributors to spermatogenic efficiency. These outcomes seem to be mediated by changes in two RNA-based processes: (i) the expression of small non-coding RNAs that are involved in the regulation of Sertoli cell function, spermatogenesis and germ cell apoptosis and (ii) alternative pre-mRNA splicing that affects the regulation of spermatogenesis but does not appear to affect germ cell apoptosis, at least during testis progression induced by undernutrition in the male sheep. These research outcomes can be extended to other animal models and are relevant to issues in human male fertility.

Human nutrition, the gut microbiome and the immune system.

Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.