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AbstractUnderstanding women’s information seeking behaviours before conception is important for the development of interventions to enhance preconception health. This project explored barriers, facilitators, and motivators towards engagement with preconception advice in women undergoing assisted reproductive technology, across BMI classifications. Twenty interviews were conducted with women attending the fertility clinic, Repromed, in South Australia. Barriers to behaviour change included challenges finding reputable information, lack of social and health provider support, and desire for secrecy. Women reported a preference for receiving health information from the internet, social media, complementary and allied health professionals. Women living with overweight reported similar behaviours and interactions. [ABSTRACT FROM AUTHOR]

Aim: This qualitative study aimed to explore the experiences of participants who were enrolled in 6‐month controlled weight loss interventions with 2‐month follow‐up to better understand the process of behaviour change and maintenance. Methods: Fifteen participants who completed or dropped out from either a daily energy restriction or intermittent fasting group were recruited using maximum variation purposive sampling. In‐depth, semi‐structured interviews were conducted at the 2‐month follow‐up phase. All interviews were transcribed and analysed using thematic analysis, guided by behaviour change models including transtheoretical model, social cognitive theory and integrated model of change. Results: Participants following both diets showed similar behaviour change patterns. Their first motivations were mostly external and relied on 'accountability' to adhere to the diet when initiating the dietary changes. Participants highlighted the importance of frequent reviews and monitoring in assisting their adherence. This feedback system promoted the development of self‐efficacy and internalised motivation to encourage an 'ownership'. Participants who transitioned successfully from relying on accountability to take 'ownership' of the intervention were more capable of tackling challenges and tailoring their diet to form a new routine for long‐term maintenance. Conclusion: External motivations were key to initiate while internalised motivations were more important to sustain the behaviour change. Health professionals can assist this process through routine monitoring and feedback processes in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Time‐restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24‐hour profiles of plasma metabolites, glucoregulatory hormones, and the subcutaneous adipose tissue (SAT) transcriptome in humans. Methods: Men (n = 15, age = 63 [4] years, BMI 30.5 [2.4] kg/m2) were recruited. A 35‐hour metabolic ward stay was conducted at baseline and after 8 weeks of 10‐hour TRE. Assessment included 24‐hour profiles of plasma glucose, nonesterified fatty acid (NEFA), triglyceride, glucoregulatory hormones, and the SAT transcriptome. Dim light melatonin onset and cortisol area under the curve were calculated. Results: TRE did not alter dim light melatonin onset but reduced morning cortisol area under the curve. TRE altered 24‐hour profiles of insulin, NEFA, triglyceride, and glucose‐dependent insulinotropic peptide and increased transcripts of circadian locomotor output cycles protein kaput (CLOCK) and nuclear receptor subfamily 1 group D member 2 (NR1D2) and decreased period circadian regulator 1 (PER1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) at 12:00 am. The rhythmicity of 450 genes was altered by TRE, which enriched in transcripts for transcription corepressor activity, DNA‐binding transcription factor binding, regulation of chromatin organization, and small GTPase binding pathways. Weighted gene coexpression network analysis revealed eigengenes that were correlated with BMI, insulin, and NEFA. Conclusions: TRE restored 24‐hour profiles in hormones, metabolites, and genes controlling transcriptional regulation in SAT, which could underpin its metabolic health benefit. [ABSTRACT FROM AUTHOR]

Human trials that compare intermittent fasting (IF) to calorie restriction (CR) with psychological, behavioral and cognition outcomes are limited. We hypothesized that there would be no difference between CR and IF on perceived eating behaviors, mood, sleep quality, quality of life (QOL) and cognition in women with overweight and obesity. In this prespecified secondary analysis of an open-label, single center, parallel assignment, randomized controlled trial, healthy women with overweight or obesity (N = 46, mean [SD] age 50 [9] years, BMI 32.9 [4.4] kg/m2), without a diagnosed eating disorder and who were randomized into 2 weight loss groups (prescribed 70% of calculated energy requirements as IF or CR) were included. Measurements were assessed in both IF and CR groups following a 12-hour overnight fast during baseline and week 8 and additionally following a 24-hour fast in the IF group only at week 8. We observed that IF produced greater weight and body fat loss than CR (P <.001). We did not detect any statistical difference between groups for the change in dietary restraint, disinhibition, hunger, mood, sleep quality, and QOL. An increase in cognitive performance was found in both IF (P =.036) and CR (P =.006) groups in one of the cognitive tasks, but there was no statistical difference between groups. Perceived eating behaviors, mood, sleep quality and cognitive performance were not changed by an acute 24-hour fast within the IF group (all P >.05). IF may be a viable alternative to CR for weight loss, in the short-term, without adversely impacting eating behaviors, mood, sleep quality, QOL or cognition in healthy women with overweight or obesity. However, larger and long term trials are required. [ABSTRACT FROM AUTHOR]

Context: Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR).Objective: In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle.Design: Seventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups).Results: IF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels.Conclusions: In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage. [ABSTRACT FROM AUTHOR]

Time-restricted feeding (TRF) initiated early during the dark phase prevents the metabolic consequences of a high-fat diet in rodent models. However, the metabolic consequences of delaying the initiation of TRF, akin to breakfast skipping in humans, is unclear. We assigned 8-week-old male C57BL/6J mice (n = 192) to chow or high-fat diet ad libitum (AL) for 4 weeks, before randomization to continue AL or 10 h of TRF, initiated at lights off (TRFe) or 4-h after lights off (TRFd) for a further 8 weeks. Oral glucose tolerance tests (1 g/kg), metabolic monitoring and body composition by echoMRI were performed, and tissues were collected at six time points. TRF reduced weight and fat mass vs AL, with a greater reduction in TRFe vs TRFd. TRF improved glucose tolerance and protected mice from high-fat diet-induced hepatosteatosis v s AL, with no difference between TRFe and TRFd. TRF increased the amplitude of Bmal1, Cry1, Per2, Nampt, and Nocturnin mRNA levels in liver. A phase delay in Bmal1, Cry1, Per2, Reverba, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight be nefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the trans lational potential of this dietary approach in humans. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the effects of intermittent fasting (IF) on mRNA levels of peripheral clock genes in skeletal muscle and subcutaneous adipose tissue (SAT) in women with obesity.Methods: Women were randomized to one of two IF protocols and provided with all foods at 100% or 70% of calculated weekly energy requirements for 8 weeks. Breakfast was consumed before a 24-hour fast, which was initiated on three nonconsecutive days per week. Muscle and SAT biopsies were performed at 8 am after an overnight fast at baseline and at week 8 on a refed day and again following a 24-hour fast at week 8 for analysis of the mRNA levels of key genes involved in circadian regulation.Results: A group-by-time interaction was observed in Per2 in muscle (F = 3.497, P = 0.044) and SAT (F = 6.686, P = 0.008), but significance was lost upon post hoc adjustment. A time effect was observed in Rorα in muscle, which was decreased by refeeding in both groups (F = 7.225, P = 0.003).Conclusions: There was no universal effect of IF to alter peripheral clocks, which may be partly because of the alignment of the fasting/feeding cycle with the biological clock. Optimizing intermittent fasting protocols could be important to prevent circadian misalignment in humans. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effects of 9-hour time-restricted feeding (TRF), early (TRFe) or delayed (TRFd), on glucose tolerance in men at risk for type 2 diabetes.Methods: Fifteen men (age 55 ± 3 years, BMI 33.9 ± 0.8 kg/m2 ) wore a continuous glucose monitor for 7 days of baseline assessment and during two 7-day TRF conditions. Participants were randomized to TRFe (8 am to 5 pm) or TRFd (12 pm to 9 pm), separated by a 2-week washout phase. Glucose, insulin, triglycerides, nonesterified fatty acids, and gastrointestinal hormone incremental areas under the curve were calculated following a standard meal on days 0 and 7 at 8 am (TRFe) or 12 pm (TRFd).Results: TRF improved glucose tolerance as assessed by a reduction in glucose incremental area under the curve (P = 0.001) and fasting triglycerides (P = 0.003) on day 7 versus day 0. However, there were no mealtime by TRF interactions in any of the variables examined. There was also no effect of TRF on fasting and postprandial insulin, nonesterified fatty acids, or gastrointestinal hormones. Mean fasting glucose by continuous glucose monitor was lower in TRFe (P = 0.02) but not TRFd (P = 0.17) versus baseline, but there was no difference between TRF conditions.Conclusions: While only TRFe lowered mean fasting glucose, TRF improved glycemic responses to a test meal in men at risk for type 2 diabetes regardless of the clock time that TRF was initiated. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition.Methods: Women with overweight (n = 88; 50 ± 1 years, BMI 32.3 ± 0.5 kg/m2 ) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic-euglycemic clamp, weight, body composition, and plasma markers were assessed following a "fed" day (12-hour fast) and a 24-hour fast (IF only).Results: IF70 displayed greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P ≤ 0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24-hour fast transiently reduced insulin sensitivity.Conclusions: When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss. [ABSTRACT FROM AUTHOR]

Protein-rich supplements are used widely for the prevention and management of malnutrition in older people. We have reported that healthy older, compared to younger, adults have less suppression of energy intake by whey-protein--effects on appetite-related hormones are unknown. The objective was to determine the effects of intraduodenally administered whey-protein on glucose, gut hormone, and amino acid concentrations, and their relation to subsequent ad libitum energy intake at a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30 kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused intraduodenally for 60 min in 10 younger (19-29 years, 73 ± 2 kg, 22 ± 1 kg/m²) and 10 older (68-81 years, 79 ± 2 kg, 26 ± 1 kg/m²) healthy men in a randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and amino acid concentrations, but not blood glucose, increased, while ghrelin decreased during the whey-protein infusions. Plasma GIP concentrations were greater in older than younger men. Energy intake correlated positively with plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon, GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which correlated to subsequent energy intake. [ABSTRACT FROM AUTHOR]

Protein-rich supplements are used widely to prevent and manage undernutrition in older people. We have previously shown that healthy older, compared to younger, adults have less suppression of energy intake by whey protein--although the effects of age on appetite-related gut hormones are largely unknown. The aim of this study was to determine and compare the acute effects of whey protein loads on blood glucose and plasma gut hormone concentrations in older and younger adults. Sixteen healthy older (eight men, eight women; mean ± SEM: age: 72 ± 1 years; body mass index: 25 ± 1 kg/m²) and 16 younger (eight men, eight women; 24 ± 1 years; 23 ± 0.4 kg/m²) adults were studied on three occasions in which they ingested 30 g (120 kcal) or 70 g (280 kcal) whey protein, or a flavored-water control drink (~2 kcal). At regular intervals over 180 min, blood glucose and plasma insulin, glucagon, ghrelin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were measured. Plasma ghrelin was dose-dependently suppressed and insulin, glucagon, CCK, GIP, and GLP-1 concentrations were dose-dependently increased by the whey protein ingestion, while blood glucose concentrations were comparable during all study days. The stimulation of plasma CCK and GIP concentrations was greater in older than younger adults. In conclusion, orally ingested whey protein resulted in load-dependent gut hormone responses, which were greater for plasma CCK and GIP in older compared to younger adults. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes continues to rise worldwide and is reaching pandemic proportions. The notion that this is due to obesity, resulting from excessive energy consumption and reduced physical activity, is overly simplistic. Circadian de-synchrony, which occurs when physiological processes are at odds with timing imposed by internal clocks, also promotes obesity and impairs glucose tolerance in mouse models, and is a feature of modern human lifestyles. The purpose of this review is to highlight what is known about glucose metabolism in animal and human models of circadian de-synchrony and examine the evidence as to whether shifts in meal timing contribute to impairments in glucose metabolism, gut hormone secretion and the risk of type 2 diabetes. Lastly, we examine whether restricting food intake to discrete time periods, will prevent or reverse abnormalities in glucose metabolism with the view to improving metabolic health in shift workers and in those more generally at risk of chronic diseases such as type 2 diabetes and cardiovascular disease. [ABSTRACT FROM AUTHOR]

We have previously identified pyloric pressures and plasma cholecystokinin (CCK) concentrations as independent determinants of energy intake following administration of intraduodenal lipid and intravenous CCK. We evaluated in healthy men whether these parameters also determine energy intake in response to intraduodenal protein, and whether, across the nutrients, any predominant gastrointestinal (GI) factors exist, or many factors make small contributions. Data from nine published studies, in which antropyloroduodenal pressures, GI hormones, and GI /appetite perceptions were measured during intraduodenal lipid or protein infusions, were pooled. In all studies energy intake was quantified immediately after the infusions. Specific variables for inclusion in a mixed-effects multivariable model for determination of independent predictors of energy intake were chosen following assessment for collinearity, and within-subject correlations between energy intake and these variables were determined using bivariate analyses adjusted for repeated measures. In models based on all studies, or lipid studies, there were significant effects for amplitude of antral pressure waves, premeal glucagon-like peptide-1 ( GLP-1) and time-to-peak GLP-1 concentrations, GLP-1 AUC and bloating scores ( P < 0.05), and trends for basal pyloric pressure (BPP), amplitude of duodenal pressure waves, peak CCK concentrations, and hunger and nausea scores (0.05 < P ≤ 0.094), to be independent determinants of subsequent energy intake. In the model including the protein studies, only BPP was identified as an independent determinant of energy intake ( P < 0.05). No single parameter was identified across all models, and effects of the variables identified were relatively small. Taken together, while GI mechanisms contribute to the regulation of acute energy intake by lipid and protein, their contribution to the latter is much less. Moreover, the effects are likely to reflect small, cumulative contributions from a range of interrelated factors. [ABSTRACT FROM AUTHOR]

Obesity prevalence continues to rise throughout the developed world, as a result of positive energy balance and reduced physical activity. At present, there is still a perception within the general community, and amongst some nutritionists, that eating multiple small meals spaced throughout the day is beneficial for weight control and metabolic health. However, intervention trials do not generally support the epidemiological evidence, and data is emerging to suggest that increasing the fasting period between meals may beneficially impact body weight and metabolic health. To date, this evidence is of short term duration, and it is becoming increasingly apparent that meal timing must also be considered if we are to ensure optimal health benefits in response to this dietary pattern. The purpose of this review is to summate the existing human literature on modifying meal frequency and timing on body weight control, appetite regulation, energy expenditure, and metabolic health under conditions of energy balance, restriction and surplus. [ABSTRACT FROM AUTHOR]

This study determined the effects of increasing loads of intraduodenal (ID) dairy protein on plasma amino acid (AA) concentrations, and their relationships with serum insulin, plasma glucagon-like peptide-1 (GLP-1) and energy intake. Sixteen healthy men had concentrations of AAs, GLP-1 and insulin measured in response to 60-min ID infusions of hydrolysed whey protein administered, in double-blinded and randomised order, at 2.1 (P2.1), 6.3 (P6.3) or 12.5 (P12.5) kJ/min (encompassing the range of nutrient emptying from the stomach), or saline control (C). Energy intake was quantified immediately afterwards. Compared with C, the concentrations of 19/20 AAs, the exception being cysteine, were increased, and this was dependent on the protein load. The relationship between AA concentrations in the infusions and the area under the curve from 0 to 60 min (AUC0-60 min) of each AA profile was strong for essential AAs (R² range, 0.61-0.67), but more variable for non-essential (0.02-0.54) and conditional (0.006-0.64) AAs. The AUC0-60 min for each AA was correlated directly with the AUC0-60 min of insulin (R² range 0.3-0.6), GLP-1 (0.2-0.6) and energy intake (0.09-0.3) (p < 0.05, for all), with the strongest correlations being for branched-chain AAs, lysine, methionine and tyrosine. These findings indicate that ID whey protein infused at loads encompassing the normal range of gastric emptying increases plasma concentrations of 19/20 AAs in a load-dependent manner, and provide novel information on the close relationships between the essential AAs, leucine, valine, isoleucine, lysine, methionine, and the conditionally-essential AA, tyrosine, with energy intake, insulin and GLP-1. [ABSTRACT FROM AUTHOR]

Proteinrich-supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69-80 yr) compared with eight young male controls (18-34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control (P ± 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2%; P ± 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls (P ± 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min; P < 0.007). Appetite decreased in young, while it increased in older (P < 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men. [ABSTRACT FROM AUTHOR]

This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in which they consumed, on 3 separate occasions, in randomised order, 450-mL drinks containing either 30 g (L) or 70 g (H) of pure whey protein isolate, or control with 0 g of protein (C). Gastric emptying, serum concentrations of AAs, ghrelin, cholecystokinin (CCK), glucagon-like-peptide 1 (GLP-1), insulin, glucagon and blood glucose were measured before and after the drinks over 180 min. Then energy intake was quantified. All AAs were increased, and 7/20 AAs were increased more by H than L. Incremental areas under the curve (iAUC0–180 min) for CCK, GLP-1, insulin and glucagon were correlated positively with iAUCs of 19/20 AAs (p < 0.05). The strongest correlations were with the branched-chain AAs as well as lysine, tyrosine, methionine, tryptophan, and aspartic acid (all R2 > 0.52, p < 0.05). Blood glucose did not correlate with any AA (all p > 0.05). Ghrelin and energy intake correlated inversely, but only weakly, with 15/20 AAs (all R2 < 0.34, p < 0.05). There is a strong relationship between gluco-regulatory hormones with a number of (predominantly essential) AAs. However, the factors mediating the effects of protein on blood glucose and energy intake are likely to be multifactorial. [ABSTRACT FROM AUTHOR]

Purpose of Review: Glucose metabolism is under circadian regulation, with insulin secretion and sensitivity being highest in the morning as compared to the evening. The present review will discuss the existing evidence for the role of meal and macronutrient timing to improve glucose metabolism and reset circadian clocks, with a focus on the evidence in humans., Recent Findings: Shortening the daily eating window (also known as time-restricted eating), or skewing food intake towards breakfast and away from the evening meal both improve glucose control in people with impaired glucose metabolism. Insulin is recently purported to be a zeitgeber and thus an important reset signal for peripheral circadian clocks in vitro and in mice. Although few studies have tested the impact of macronutrient timing in humans, eating a greater proportion of carbohydrates earlier, rather than later, in the day is associated with better glucose control., Summary: The impact of carbohydrate intake timing on endogenous central and peripheral clocks, and its potential to optimize circadian regulation and improve glycaemic control, are not well understood but are currently under intense exploration., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Impaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR)., Objective: In a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle., Design: Seventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups)., Results: IF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels., Conclusions: In comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unbiased and sensitive quantification of low abundance small proteins in human plasma ( e.g. hormones, immune factors, metabolic regulators) remains an unmet need. These small protein factors are typically analyzed individually and using antibodies that can lack specificity. Mass spectrometry (MS)-based proteomics has the potential to address these problems, however the analysis of plasma by MS is plagued by the extremely large dynamic range of this body fluid, with protein abundances spanning at least 13 orders of magnitude. Here we describe an enrichment assay (SPEA), that greatly simplifies the plasma dynamic range problem by enriching small-proteins of 2-10 kDa, enabling the rapid, specific and sensitive quantification of >100 small-protein factors in a single untargeted LC-MS/MS acquisition. Applying this method to perform deep-proteome profiling of human plasma we identify C5ORF46 as a previously uncharacterized human plasma protein. We further demonstrate the reproducibility of our workflow for low abundance protein analysis using a stable-isotope labeled protein standard of insulin spiked into human plasma. SPEA provides the ability to study numerous important hormones in a single rapid assay, which we applied to study the intermittent fasting response and observed several unexpected changes including decreased plasma abundance of the iron homeostasis regulator hepcidin., (© 2019 Harney et al.)

Protein-rich supplements are used widely to prevent and manage undernutrition in older people. We have previously shown that healthy older, compared to younger, adults have less suppression of energy intake by whey protein-although the effects of age on appetite-related gut hormones are largely unknown. The aim of this study was to determine and compare the acute effects of whey protein loads on blood glucose and plasma gut hormone concentrations in older and younger adults. Sixteen healthy older (eight men, eight women; mean ± SEM: age: 72 ± 1 years; body mass index: 25 ± 1 kg/m²) and 16 younger (eight men, eight women; 24 ± 1 years; 23 ± 0.4 kg/m²) adults were studied on three occasions in which they ingested 30 g (120 kcal) or 70 g (280 kcal) whey protein, or a flavored-water control drink (~2 kcal). At regular intervals over 180 min, blood glucose and plasma insulin, glucagon, ghrelin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were measured. Plasma ghrelin was dose-dependently suppressed and insulin, glucagon, CCK, GIP, and GLP-1 concentrations were dose-dependently increased by the whey protein ingestion, while blood glucose concentrations were comparable during all study days. The stimulation of plasma CCK and GIP concentrations was greater in older than younger adults. In conclusion, orally ingested whey protein resulted in load-dependent gut hormone responses, which were greater for plasma CCK and GIP in older compared to younger adults., Competing Interests: The authors declare no conflict of interest.

Intraduodenal infusion of lipid or protein potently reduces subsequent energy intake. There is evidence that the underlying mechanisms differ significantly between the two nutrients. While intraduodenal lipid stimulates glucagon-like peptide-1 and CCK much more than protein, the release of insulin and glucagon is substantially greater in response to protein. Ghrelin and PYY are both involved in short-term regulation, while leptin is a long-term regulator, of energy balance; the acute effects of nutrients on leptin release are unclear. We investigated the comparative effects of intraduodenal lipid and protein on plasma ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three separate days. Blood samples were collected at baseline and regularly during infusions. Both lipid and protein potently suppressed plasma ghrelin compared with control (both P < 0.001), with no difference between them. While both lipid and protein stimulated plasma PYY (P < 0.001), the effect of lipid was substantially greater than that of protein (P < 0.001). Neither intraduodenal lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and protein have discrepant effects on the release of PYY, but not ghrelin. When considered with our previous findings, it appears that, with the exception of ghrelin, the energy intake-suppressant effects of lipid and protein are mediated by different mechanisms., (Copyright © 2015 the American Physiological Society.)