Leptin as a key regulator of the adipose organ.

Leptin is a hormone primarily produced by the adipose tissue in proportion to the size of fat stores, with a primary function in the control of lipid reserves. Besides adipose tissue, leptin is also produced by other tissues, such as the stomach, placenta, and mammary gland. Altogether, leptin exerts a broad spectrum of short, medium, and long-term regulatory actions at the central and peripheral levels, including metabolic programming effects that condition the proper development and function of the adipose organ, which are relevant for its main role in energy homeostasis. Comprehending how leptin regulates adipose tissue may provide important clues to understand the pathophysiology of obesity and related diseases, such as type 2 diabetes, as well as its prevention and treatment. This review focuses on the physiological and long-lasting regulatory effects of leptin on adipose tissue, the mechanisms and pathways involved, its main outcomes on whole-body physiological homeostasis, and its consequences on chronic diseases.

Breast Milk MicroRNAs Related to Leptin and Adiponectin Function Can Be Modulated by Maternal Diet and Influence Offspring Phenotype in Rats.

There is evidence of the role of milk components in the metabolic programming of offspring. Here, we aimed to investigate the effects of a diet during lactation on breast milk leptin, adiponectin, and related miRNAs' expression, and their impact on dams and their offspring. Dams were fed a control diet (controls) or a diet enriched with oleic acid, betaine, and leucine (TX) throughout lactation. A TX diet promoted higher leptin at lactation day (LD) five and lower adiponectin on LD15 (vs. controls) in milk, resulting in increased leptin to adiponectin (L/A) ratio throughout lactation. Moreover, TX diet reduced milk levels of miR-27a, miR-103, miR-200a, and miR-222. Concerning TX offspring, higher body fat was early observed and maintained into adult life, accompanied by higher HOMA-IR than controls at three months of age. Offspring body fat content in adulthood correlated positively with milk L/A ratio at LD15 and negatively with miRNAs modulated by the TX diet. In conclusion, maternal diet during lactation can modulate leptin and adiponectin interplay with miRNAs in milk, setting up the metabolic programming of the offspring. Better knowledge about the influence of diet on this process is necessary to promote a healthy adult life in the progeny.

Identification of blood cell transcriptome-based biomarkers in adulthood predictive of increased risk to develop metabolic disorders using early life intervention rat models.

Calorie restriction during gestation in rats has long-lasting adverse effects in the offspring. It induces metabolic syndrome-related alterations, which are partially reversed by leptin supplementation during lactation. We employed these conditions to identify transcript-based nutrient sensitive biomarkers in peripheral blood mononuclear cells (PBMCs) predictive of later adverse metabolic health. The best candidate was validated in humans. Transcriptome analysis of PBMCs from adult male Wistar rats of three experimental groups was performed: offspring of control dams (CON), and offspring of 20% calorie-restricted dams during gestation without (CR) and with leptin supplementation throughout lactation (CR-LEP). The expression of 401 genes was affected by gestational calorie restriction and reversed by leptin. The changes preceded metabolic syndrome-related phenotypic alterations. Of these genes, Npc1 mRNA levels were lower in CR vs CON, and normalized to CON in CR-LEP. In humans, NPC1 mRNA levels in peripheral blood cells (PBCs) were decreased in subjects with mildly impaired metabolic health compared to healthy subjects. Therefore, a set of potential transcript-based biomarkers indicative of a predisposition to metabolic syndrome-related alterations were identified, including NPC1, which was validated in humans. Low NPC1 transcript levels in PBCs are a candidate biomarker of increased risk for impaired metabolic health in humans.

Metabolomic approach in milk from calorie-restricted rats during lactation: a potential link to the programming of a healthy phenotype in offspring.

PURPOSE: Mild/moderate maternal calorie restriction during lactation in rats has been associated with a lower predisposition to obesity and a healthier metabolic profile in adult offspring. Here, we aimed to assess the impact of maternal calorie restriction during lactation on milk composition to identify potential candidate components that could be involved in the programming effects in offspring. METHODS: An untargeted metabolomic approach in milk samples from 20%-calorie-restricted lactating (CRL) dams and their controls was performed. Levels of leptin, adiponectin, and irisin hormones in milk were also determined at lactating days 5, 10, and 15. RESULTS: Metabolomic analyses revealed a different metabolite pattern in milk between controls and CRL dams. 29 differential metabolites were tentatively identified (p < 0.05, FC > 1.5). Among them, myo-inositol, which showed greater levels in milk from CRL rats than controls, may be highlighted as one of the biologically plausible candidates that could be related to the beneficial effects of CRL in offspring. Results regarding myo-inositol were validated spectrophotometrically at days 10 and 15 of lactation, and levels in milk were correlated with maternal plasma levels. In addition, milk from CRL dams presented increased levels of adiponectin, decreased levels of irisin, and no changes in leptin levels vs controls throughout lactation. CONCLUSION: These data reveal important changes in milk composition due to calorie restriction during lactation that may be involved in the metabolic programming of the healthier phenotype of adult offspring. However, the possible contribution of the specific components is yet to be determined.

Blood cell transcript levels in 5-year-old children as potential markers of breastfeeding effects in those small for gestational age at birth.

BACKGROUND: Nutrition of the newborn during the early postnatal period seems to be of capital importance and there is clinical evidence showing the protective effect of breastfeeding compared with formula feeding on childhood obesity and its comorbidities. Infants born small for gestation age may be more sensitive to the type of feeding during lactation. Here, we aimed to analyze the impact of birth weight and the type of infant feeding on the expression levels in peripheral blood cells of selected candidate genes involved in energy homeostasis in 5-year-old children, to find out potential early biomarkers of metabolic programming effects during this period of metabolic plasticity. METHODS: Forty subjects were recruited at birth and divided in four groups according to birth weight (adequate or small for gestational age) and type of infant feeding (breastfeeding or formula feeding). They were followed from birth to the age of 5 years. RESULTS: At 5 years, no significant differences regarding anthropometric parameters were found between groups, and all children had normal biochemical values. Expression levels of UCP2 and MC4R in peripheral blood cells were lower and higher, respectively, in formula feeding children compared with breastfeeding ones (P = 0.002 and P = 0.064, two-way ANOVA). Differences were more marked and significant by Student's t test in small for gestation age children (P < 0.001 and P = 0.017, respectively). Transcript levels of FASN and FTO in peripheral blood cells were also different according to the type of infant feeding, but only in small for gestation age children. CONCLUSIONS: Altogether, these results suggest that small for gestation age infants are more sensitive to the type of feeding during lactation, and transcript levels of particular genes in peripheral blood cells, especially the MC4R/UCP2 mRNA ratio, may precisely reflect these effects in the absence of clear differences in phenotypic traits.

Enhancing hepatic fatty acid oxidation as a strategy for reversing metabolic disorders programmed by maternal undernutrition during gestation.

BACKGROUND/AIMS: Moderate maternal calorie-restriction during gestation programmes offspring for a major propensity to develop metabolic alterations in adulthood. We aimed to assess whether increased hepatic fatty-acid oxidation (FAO), at early ages, by gene transfer of Cpt1am (active mutant of carnitine palmitoyltransferase-1a), may be a strategy for reversing metabolic disturbances associated to maternal calorie-restriction during gestation in rats. METHODS: AAV-Gfp (control) and AAV-Cpt1am vectors were administered by tail vein injection in 18-day-old control-pups and the offspring of 20% calorie-restricted rats during gestation (CR). After weaning, animals were fed with normal-fat diet. At the age of 4 months, they were moved to HF-diet and sacrificed at the age of 6 months to collect tissues. Locomotive activity, energy expenditure and blood pressure were measured. RESULTS: Under HF-diet, CR-animals showed higher HOMA-IR, adipocyte diameter and hepatic triglyceride accumulation than controls; these alterations were reverted in Cpt1am-injected animals. In liver, this treatment ameliorated inflammatory state, decreased expression of lipogenesis-related genes and partially restored the decreased expression of leptin-receptor occurring in CR-animals. Treatment also reverted the decreased energy expenditure and the increased blood pressure of CR-animals. CONCLUSION: Increasing hepatic FAO through AAV-Cpt1am injection at juvenile ages prevents some metabolic disorders associated to gestational maternal calorie-restriction.

Brain-Derived Neurotrophic Factor as a Potential Mediator of the Beneficial Effects of Myo-Inositol Supplementation during Suckling in the Offspring of Gestational-Calorie-Restricted Rats.

This study aims to investigate the potential mechanisms underlying the protective effects of myo-inositol (MI) supplementation during suckling against the detrimental effects of fetal energy restriction described in animal studies, particularly focusing on the potential connections with BDNF signaling. Oral physiological doses of MI or the vehicle were given daily to the offspring of control (CON) and 25%-calorie-restricted (CR) pregnant rats during suckling. The animals were weaned and then fed a standard diet until 5 months of age, when the diet was switched to a Western diet until 7 months of age. At 25 days and 7 months of age, the plasma BDNF levels and mRNA expression were analyzed in the hypothalamus and three adipose tissue depots. MI supplementation, especially in the context of gestational calorie restriction, promoted BDNF secretion and signaling at a juvenile age and in adulthood, which was more evident in the male offspring of the CR dams than in females. Moreover, the CR animals supplemented with MI exhibited a stimulated anorexigenic signaling pathway in the hypothalamus, along with improved peripheral glucose management and enhanced browning capacity. These findings suggest a novel connection between MI supplementation during suckling, BDNF signaling, and metabolic programming, providing insights into the mechanisms underlying the beneficial effects of MI during lactation.

Metabolic programming of sirtuin 1 (SIRT1) expression by moderate energy restriction during gestation in rats may be related to obesity susceptibility in later life.

In rats, 20% gestational energy restriction programmes offspring for higher food intake, which in adulthood results in higher body weight in males but not in females. Here, we aimed to assess whether the effects of moderate energy restriction during gestation and the sex-related outcomes on adult body weight may be related to the metabolic programming of sirtuin expression in different tissues. For this purpose, 25-d-old offspring of control and 20% energy-restricted (ER) rats (from days 1-12 of pregnancy) were studied. Body weight and the weight of white adipose tissue (WAT) depots and liver were recorded and mRNA expression of sirtuin 1 (SIRT1) and selected genes in the WAT, liver, muscle and hypothalamus were analysed. No differences were found in body weight or the weight of WAT and liver between the control and ER animals. A similar pattern of SIRT1 mRNA expression was found in the WAT, liver and skeletal muscle of ER animals, but in a sex-dependent manner: ER males showed lower SIRT1 mRNA levels than the controls, while no differences were found in females. A sex-different pattern was also observed in the hypothalamus. ER males, but not females, also showed lower mRNA levels of adipose TAG lipase (ATGL) and uncoupling protein 2 in WAT and of sterol response element binding protein 1c and stearoyl-CoA desaturase-1 in the liver. Both sexes of ER animals showed lower mRNA levels of 5' adenosine monophosphate-activated protein kinase and ATGL in the liver. In conclusion, moderate maternal energy restriction during gestation programmes a particular, sex-dependent gene expression profile of SIRT1 in different peripheral tissues, which may be related to obesity predisposition in adulthood; therefore SIRT1 expression emerges as a potential early biomarker of obesity susceptibility.

Influence of Maternal Metabolic Status and Diet during the Perinatal Period on the Metabolic Programming by Leptin Ingested during the Suckling Period in Rats.

We aimed to analyze the long-term metabolic effects of leptin supplementation at physiological doses during suckling in the offspring of diet-induced obese rats, together with the potential benefits of improving maternal diet during lactation. Thus, the offspring of: dams fed standard-diet (SD) (CON-dams), dams fed western-diet (WD) before and during gestation and lactation (WD-dams), and dams fed as WD-dams but moved to SD during lactation (REV-dams) were supplemented throughout suckling with leptin or vehicle, and fed SD or WD from weaning to four months. Under SD, leptin treatment significantly improved metabolic profile and body fat accumulation, with stronger effects in the male offspring of CON-dams and REV-dams. Under WD, the offspring of WD-dams presented metabolic alterations that were not evident in the offspring of REV-dams. Moreover, leptin supplementation improved glucose homeostasis in the male offspring of REV-dams. Conversely, leptin supplementation in females born to WD-dams and fed WD from weaning resulted in impaired insulin sensitivity and increased hepatic lipid content. These results highlight the importance of a balanced maternal diet during the perinatal period, especially lactation, for the subsequent metabolic health of the offspring and for the beneficial effects of leptin supplementation during suckling, more evident in the male offspring.

A Diet Profiling Algorithm (DPA) to Rank Diet Quality Suitable to Implement in Digital Tools-A Test Study in a Cohort of Lactating Women.

Although nutrient profiling systems can empower consumers towards healthier food choices, there is still a need to assess diet quality to obtain an overall perspective. The purpose of this study was to develop a diet profiling algorithm (DPA) to evaluate nutritional diet quality, which gives a final score from 1 to 3 with an associated color (green-yellow-orange). It ranks the total carbohydrate/total fiber ratio, and energy from saturated fats and sodium as potentially negative inputs, while fiber and protein are assumed as positive items. Then, the total fat/total carbohydrate ratio is calculated to evaluate the macronutrient distribution, as well as a food group analysis. To test the DPA performance, diets of a lactating women cohort were analyzed, and a correlation analysis between DPA and breast milk leptin levels was performed. Diets classified as low quality showed a higher intake of negative inputs, along with higher energy and fat intakes. This was reflected in body mass index (BMI) and food groups, indicating that women with the worst scores tended to choose tastier and less satiating foods. In conclusion, the DPA was developed and tested in a sample population. This tool can be easily implemented in digital nutrition platforms, contributing to real-time dietary follow-up of patients and progress monitoring, leading to further dietary adjustment.

Stachydrine, N-acetylornithine and trimethylamine N-oxide levels as candidate milk biomarkers of maternal consumption of an obesogenic diet during lactation.

We aimed to evaluate whether improving maternal diet during lactation in diet-induced obese rats reverts the impact of western diet (WD) consumption on the metabolome of milk and offspring plasma, as well as to identify potential biomarkers of these conditions. Three groups of dams were followed: control-dams (CON-dams), fed with standard diet (SD); WD-dams, fed with WD prior and during gestation and lactation; and reversion-dams (REV-dams), fed as WD-dams but moved to SD during lactation. Metabolomic analysis was performed in milk at lactation days 5, 10, and 15, and in plasma from their male and female offspring at postnatal day 15. Milk of WD-dams presented, throughout lactation and compared to CON-dams, altered profiles of amino acids and of the carnitine pool, accompanied by changes in other polar metabolites, being stachydrine, N-acetylornithine, and trimethylamine N-oxide the most relevant and discriminatory metabolites between groups. The plasma metabolome profile was also altered in the offspring of WD-dams in a sex-dependent manner, and stachydrine, ergothioneine and the acylcarnitine C12:1 appeared as the top three most discriminating metabolites in both sexes. Metabolomic changes were largely normalized to control levels both in the milk of REV-dams and in the plasma of their offspring. We have identified a set of polar metabolites in maternal milk and in the plasma of the offspring whose alterations may indicate maternal intake of an unbalanced diet during gestation and lactation. Levels of these metabolites may also reflect the beneficial effects of implementing a healthier diet during lactation.

Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv).

Background: Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health. Methods/design: The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal (n = 90), and postpubertal adolescents (n = 90). Each group will include three subgroups (n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers. Discussion: The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers' responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT05907785.

Implementation of a healthy diet to lactating rats attenuates the early detrimental programming effects in the offspring born to obese dams. Putative relationship with milk hormone levels.

Lactation is a critical period of development and alterations in milk composition due to maternal diet or status may affect infant growth. We aimed to evaluate in rats whether improving maternal nutrition during lactation attenuates early imprinted adverse metabolic effects in the offspring born to obese dams. Three groups were studied: Control (C) dams, fed with standard diet; Western diet (WD) dams, fed with WD 1 month prior to gestation and during gestation and lactation; and Reversion (Rev) dams, fed as WD-dams, but moved to a standard diet during lactation. Macronutrient content, insulin, leptin and adiponectin levels were determined in milk. Phenotypic traits and circulating parameters in dams and their offspring were determined throughout lactation. Results showed that, at weaning, WD-dams displayed lower body weight and greater plasma insulin and non-esterified fatty acids levels than C-dams, and signs of hepatic steatosis. Milk from WD-dams showed lower protein content and insulin, leptin, and adiponectin levels during the entire or the late lactation. Rev-dams retained excess body fat content, but milk composition and most circulating parameters were not different from controls at late lactation and showed higher leptin mRNA levels in mammary gland than WD-dams. The offspring of WD-dams, but not that of Rev-dams, displayed higher body weight, adiposity, and circulating leptin and glucose levels than controls at weaning. In conclusion, dietary improvement during lactation prevents early adverse effects in offspring associated with maternal intake of an obesogenic diet, that may be related with the normalization of milk hormone levels.

Dietary Improvement during Lactation Normalizes miR-26a, miR-222 and miR-484 Levels in the Mammary Gland, but Not in Milk, of Diet-Induced Obese Rats.

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control group), with a Western diet (WD) prior to and during gestation and lactation (WD group), or with WD prior to and during gestation but moved to SD during lactation (Rev group) were followed. The WD group showed higher miR-26a, miR-222 and miR-484 levels than the controls in the MG, but the miRNA profile in Rev animals was not different from those of the controls. The WD group also displayed higher miR-125a levels than the Rev group. Dams of the WD group, but not the Rev group, displayed lower mRNA expression levels of Rb1 (miR-26a's target) and Elovl6 (miR-125a's target) than the controls in the MG. The WD group also presented lower expression of Insig1 (miR-26a's target) and Cxcr4 (miR-222's target) than the Rev group. However, both WD and Rev animals displayed lower expression of Vegfa (miR-484's target) than the controls. WD animals also showed greater miR-26a, miR-125a and miR-222 levels in the milk than the controls, but no differences were found between the WD and Rev groups. Thus, implementation of a healthy diet during lactation normalizes the expression levels of specific miRNAs and some target genes in the MG of diet-induced obese dams but not in milk.

Reverting to a Healthy Diet during Lactation Normalizes Maternal Milk Lipid Content of Diet-Induced Obese Rats and Prevents Early Alterations in the Plasma Lipidome of the Offspring.

SCOPE: This study aims to assess in rats whether normalizing maternal diet during lactation prevents the harmful effects of western diet (WD) consumption during the whole perinatal period on the lipidomic profile in maternal milk and offspring plasma. METHODS AND RESULTS: Control dams (CON-dams), fed with standard diet (SD); WD-dams, fed with WD prior and during gestation and lactation; and reversion dams (REV-dams), fed as WD-dams but moved to SD during lactation are followed. Lipidomic analysis is performed in milk and plasma samples from pups. Milk of WD-dams presents a different triacylglycerol composition and free fatty acid (FA) profile compared to CON-dams, including an increased ratio of pro-inflammatory to anti-inflammatory long-chain polyunsaturated FA. Such alterations, which are also present in the plasma of their offspring, are widely reversed in the milk of REV-dams and the plasma of their pups. This is related with the recovery of control adiponectin expression levels in the mammary gland, and the presence of decreased expression of pro-inflammatory factors. CONCLUSION: Implementing a healthy diet during lactation prevents early alterations in the plasma lipidome of pups associated to the maternal intake of an obesogenic diet, which may be related to the normalization of milk lipid content and the inflammatory state in the mammary gland.

Empowering consumers to PREVENT diet-related diseases through OMICS sciences (PREVENTOMICS): protocol for a parallel double-blinded randomised intervention trial to investigate biomarker-based nutrition plans for weight loss.

INTRODUCTION: Personalised nutrition holds immense potential over conventional one-size-fits-all approaches for preventing and treating diet-related diseases, such as obesity. The current study aims to examine whether a personalised nutritional plan produces more favourable health outcomes than a standard approach based on general dietary recommendations in subjects with overweight or obesity and elevated waist circumference. METHODS AND ANALYSIS: This project is a 10-week parallel, double-blinded randomised intervention trial. We plan to include 100 adults aged 18-65 years interested in losing weight, with body mass index ≥27 but<40 kg/m2 and elevated waist circumference (males >94 cm; females >80 cm). Participants will be categorised into one of five predefined 'clusters' based on their individual metabolic biomarker profile and genetic background, and will be randomised in a 1:1 ratio to one of two groups: (1) personalised plan group that will receive cluster-specific meals every day for 6 days a week, in conjunction with a personalised behavioural change programme via electronic push notifications; or (2) control group that will receive meals following the general dietary recommendations in conjunction with generic health behaviour prompts. The primary outcome is the difference between groups (personalised vs control) in the change in fat mass from baseline. Secondary outcomes include changes in weight and body composition, fasting blood glucose and insulin, lipid profile, adipokines, inflammatory biomarkers, and blood pressure. Other outcomes involve measures of physical activity and sleep patterns, health-related quality of life, dietary intake, eating behaviour, and biomarkers of food intake. The effect of the intervention on the primary outcome will be analysed by means of linear mixed models. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated through peer-reviewed publications, conference presentations and media outlets. TRIAL REGISTRATION NUMBER: NCT04590989.

A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study.

BACKGROUND & AIMS: Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform-which uses metabolomic and genetic information to classify individuals into different 'metabolic clusters' and create personalized dietary plans-for improving health outcomes in subjects with overweight or obesity. METHODS: A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18-65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior. RESULTS: There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: -2.1 [95% CI -2.9, -1.4] kg; control: -2.0 [95% CI -2.7, -1.3] kg) and body weight (personalized: -3.1 [95% CI -4.1, -2.1] kg; control: -3.3 [95% CI -4.2, -2.4] kg). The difference between groups in fat mass change was -0.1 kg (95% CI -1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups. CONCLUSION: Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov registry (NCT04590989).

Leptin and Metabolic Programming.

This Special Issue of Nutrients "Leptin and Metabolic Programming" includes one review article regarding the function of leptin throughout the entire life on cardiometabolic fates and four original articles related to the new function of leptin present in milk and liquid amniotic, its possible relation with other components of breast milk, and how environmental conditions may impact on leptin action and metabolic programming [...].

Absorption, Distribution, Metabolism, and Excretion of the Main Olive Tree Phenols and Polyphenols: A Literature Review.

The effects of olive tree (poly)phenols (OPs) are largely dependent upon their bioavailability and metabolization by humans. Absorption, distribution, metabolism, and excretion (ADME) are fundamental for the nutritional efficacy and toxicological impact of foods containing OPs. This review includes studies on the administration of hydroxytyrosol (HT), oleuropein (Ole), or other OPs and foods, products, or mixtures that contain them. Briefly, data from in vivo studies indicate that OPs are absorbable by intestinal cells. Both absorption and bioavailability depend upon each compound and/or the matrix in which it is contained. OPs metabolism begins in enterocytes and can also continue in the liver. Metabolic phase I mainly consists of the hydrolysis of Ole, which results in an increase in the HT content. Phase II metabolic reactions involve the conjugation of (poly)phenols mainly with glucuronide and sulfate groups. This review offers a complete perspective of the ADME processes of OPs, which could support the future nutritional and/or toxicological studies in this area.

Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects.

We studied whether myo-inositol supplementation throughout lactation, alone and combined with leptin, may reverse detrimental effects on hypothalamic structure and function caused by gestational calorie gestation (CR) in rats. Candidate early transcript-based biomarkers of metabolic health in peripheral blood mononuclear cells (PBMC) were also studied. Offspring of dams exposed to 25% gestational CR and supplemented during lactation with physiological doses of leptin (CR-L), myo-inositol (CR-M), the combination (CR-LM), or the vehicle (CR-V) as well as control rats (CON-V) were followed and sacrificed at postnatal day 25. Myo-inositol and the combination increased the number of neurons in arcuate nucleus (ARC) (only in females) and paraventricular nucleus, and myo-inositol (alone) restored the number of αMSH+ neurons in ARC. Hypothalamic mRNA levels of Lepr in CR-M and Insr in CR-M and CR-LM males were higher than in CR-V and CON-V, respectively. In PBMC, increased expression levels of Lrp11 and Gls in CR-V were partially normalized in all supplemented groups (but only in males for Gls). Therefore, myo-inositol supplementation throughout lactation, alone and combined with leptin, reverts programmed alterations by fetal undernutrition on hypothalamic structure and gene expression of potential early biomarkers of metabolic health in PBMC, which might be attributed, in part, to increased leptin sensitivity.