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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., (© 2023 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.)

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/m 2 ) 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., (© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

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/m 2 ), 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., Competing Interests: Author Declarations The authors declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

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 vs 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, Reverbα, Nampt, NAD, Sirt1, and Nocturnin was observed in TRFd. Thus, delaying TRF limited the weight benefit and induced a phase delay in the hepatic clock, but improved metabolic health. Allowing more flexibility in when TRF is initiated may increase the translational potential of this dietary approach in humans.

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., (© 2020 The Obesity Society.)

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.

Selenoprotein P (SeP) is secreted primarily by the liver and postulated to cause insulin resistance. The aim of this study was to measure plasma SeP in individuals who are lean (N=29) or overweight/obese (N=34), and examine relationships between circulating SeP, SEPP1 (SeP, plasma 1) expression in subcutaneous adipose tissue, and markers of insulin resistance. SeP was higher in individuals who were overweight/obese (P<0.001), and associated with insulin resistance by HOMA-IR and by clamp, but not independently of BMI. SEPP1 mRNA was correlated negatively with BMI, suggesting there may be tissue specific regulation. This study suggests that obesity, rather than insulin resistance, is central to the increase in SeP., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Background: In lean individuals, intraduodenal protein and lipid modulate gastrointestinal motor and hormone functions and reduce energy intake in a load-dependent manner; protein also stimulates insulin, with modest effects on reducing blood glucose. The effect of intraduodenal lipid on gastrointestinal motor and hormone responses is diminished in obesity; whether the effects of protein are also attenuated remains unclear., Objectives: The objectives of this study were to characterize the load-dependent effects of intraduodenal whey protein hydrolysate on antropyloroduodenal pressures, gut hormones, glycemia, appetite, and energy intake in obese subjects and to compare the responses to the higher protein load with those in lean subjects., Design: We measured antropyloroduodenal pressures, plasma cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, blood glucose, appetite, and energy intake in 12 nondiabetic obese men on 3 separate occasions, in a double-blind, randomized order, during 60-min intraduodenal infusions of hydrolyzed whey protein at either 0 (saline control), 1.5, or 3 kcal/min. Twelve age-matched lean individuals received a 3-kcal/min infusion only. Immediately after the infusions, energy intake from a buffet lunch was quantified., Results: In obese subjects, protein suppressed antral and duodenal pressures; stimulated plasma CCK, GLP-1, GIP, insulin, and glucagon (all r > 0.57, P < 0.01); and tended to reduce energy intake (r = -10.38, P = 0.057) in a dose-dependent manner. In response to the 3-kcal/min protein load, antropyloroduodenal pressures, CCK, GLP-1, and glucagon did not differ between lean and obese subjects. Insulin release was greater, and GIP release less, in obese than in lean subjects (both P < 0.05), whereas the reduction in glucose was comparable. Energy intake tended to be higher in obese subjects (P = 0.08)., Conclusions: The gastrointestinal effects of hydrolyzed whey protein remain relatively intact in obesity; however, the observed changes in insulin and GIP suggest early disturbances in the insulin-incretin axis. This study was registered at www.anzctr.org.au as ACTRN 12612000203853., (© 2015 American Society for Nutrition.)

Growth differentiation factor 15 (GDF15) increases with acute fast in animals, and high GDF15 reduces food intake in rodents. We explored whether GDF15 was altered following intermittent fasting (IF) versus caloric restriction (CR), and associations with energy intake. Females with obesity received all foods at 70% (IF70 and CR70) or 100% of energy requirements for 8 weeks. IF ate 2–9% less than provided on refeeding days, resulting in greater weight losses. GDF15 was increased 5% more in IF70 versus CR70, but not associated with energy intake. This rise in GDF15 is unlikely to explain restriction of energy intake during IF. [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]

Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study (D aily versus I ntermittent R estriction of E nergy: C ontrolled T rial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. Anticipated 260 non-diabetic men and women aged 35–75 years, BMI 25−50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

• Energy restricted intermittent fasting reduces greater body weight and fat mass. • Daily calorie restriction does not alter systemic, fat and muscle inflammation. • Intermittent fasting transiently increases systemic, fat and muscle inflammation. • Adipose tissue macrophages are linked with lipolysis in response to a 24-h fast. This study compared the effects of daily calorie restriction (DR) versus intermittent fasting (IF) on markers of inflammation and extracellular matrix deposition in adipose tissue and skeletal muscle in a controlled feeding trial in women with overweight or obesity. Women (N = 76) were randomised to one of three diets and provided with all foods at 100% (IF100) or 70% (IF70 and DR70) of calculated energy requirements for 8 weeks. IF groups ate breakfast prior to fasting for 24-h on 3 non-consecutive days/week. Weight, body composition, serum non-esterified fatty acids (NEFA), tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), M1- and M2-macrophage markers by qPCR and immunohistochemistry in adipose tissue and skeletal muscle were measured following a 12-h overnight fast (fed day, all groups) and a 24-h fast (IF groups only). IF70 resulted in greater weight and fat losses and reductions in serum NEFA versus DR70 and IF100 (P < 0.05) after fed days. Markers of inflammation in serum (TNFα, IL6 and IL10), subcutaneous adipose tissue and skeletal muscle (CD68, CD40 and CD163) were unchanged by DR or IF after fed days. After fasting, NEFA, M1-macrophages (CD40+) in adipose tissue, and M2-macrophages (CD163+) in muscle were increased in IF70 and IF100 (all P < 0.05) and the changes in NEFA and mRNA of pan-macrophage marker CD68 in adipose tissue were positively correlated (r = 0.56, P = 0.002). Unlike caloric restriction, IF transiently elevated markers of macrophage infiltration in adipose tissue and skeletal muscle, possibly in response to marked increases in adipose tissue lipolysis. [ABSTRACT FROM AUTHOR]

Background Skeletal muscle extracellular matrix (ECM) remodeling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. The aim of the current study was to examine the timeline of this response and determine whether 3 and 28 days of overfeeding alters markers of ECM turnover. Methods Forty healthy individuals were overfed by 1250 kcal/day for 28 days. Hyperinsulinemic–euglycemic clamps and abdominal fat distribution were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28. mRNA expression (COL1a1, COL3a1, MMP2, MMP9, TIMP1, CD68, Integrin) was performed in 19 subjects that consented to having all biopsies performed and microarray analysis was performed in 8 participants at baseline and day 28. Results In the whole cohort, body weight increased by 0.6 ± 0.1 and 2.7 ± 0.3 kg at days 3 and 28 (both P < 0.001), respectively. Glucose infusion rate during the hyperinsulinemic–euglycemic clamp decreased from 54.8 ± 2.8 at baseline to 50.3 ± 2.5 μmol/min/kg FFM at day 28 of overfeeding (P = 0.03). Muscle COL1 and COL3 and MMP2 mRNA levels were significantly higher 28 days after overfeeding (all P < 0.05), with no significant changes in MMP9, TIMP1, CD68 and integrin expression. Microarray based gene set tests revealed that pathways related to ECM receptor interaction, focal adhesion and adherens junction were differentially altered. Conclusions Skeletal muscle ECM remodeling occurs early in response to over-nutrition with as little as 3% body weight gain. Our findings contribute to the growing evidence linking muscle ECM remodeling and accumulation as another sequela of obesity-related insulin resistance. [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]

Background: In healthy individuals, intraduodenal whey protein load-dependently modulates gastrointestinal motor and hormonal functions and suppresses energy intake. The effect of oral whey, particularly the impact of load, has not been evaluated. Objective: The purpose of this study was to quantify gastric emptying of 30 and 70 g of oral whey protein loads and their relation to gastrointestinal hormone, glycemic, and appetitive responses. Design: On 3 separate occasions in a randomized, double-blind order, 18 lean men [mean ± SEM age: 24.8 ± 1.4 y; body mass index (in kg/m ): 21.6 ± 0.5] received iso-osmolar, equally palatable drinks (~450 mL) containing 30 g pure whey protein isolate (L), 70 g pure whey protein isolate (H), or saline (control). Gastric emptying (with the use of 3-dimensional ultrasound), plasma cholecystokinin, glucagon-like peptide 1, glucose-dependent in-sulinotropic peptide, insulin, glucagon, total amino acids, and blood glucose were measured for 180 min after consumption of the drinks, and energy intake at a buffet-style lunch was quantified. Results: Gastric emptying of the L and H drinks was comparable when expressed in kilocalories per minute (L: 2.6 ± 0.2 kcal/min; H: 2.9 ± 0.3 kcal/min) and related between individuals (r = 0.54, P < 0.01). Gastrointestinal hormone, insulin, and glucagon responses to the L and H drinks were comparable until ~ 45-60 min after ingestion, after which time the responses became more differentiated. Blood glucose was modestly reduced after the H drink between t = 45 and 150 min when compared with the L drink (all P < 0.05). Energy intake was suppressed by both L and H drinks compared with control (P < 0.05) (control: 1174 ± 91 kcal; L: 1027 ± 81 kcal; and H: 997 ± 71 kcal). Conclusion: These findings indicate that, in healthy lean men, the rate of gastric emptying of whey protein is independent of load and determines the initial gastrointestinal hormone response. This study was registered at www.anzctr.org.au as 12611000706976. [ABSTRACT FROM AUTHOR]