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Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.

This study was designed to determine a cutoff point for identifying insulin resistance from hyperinsulinemic-euglycemic clamp studies performed at 120 mU/m(2)·min in a white population and to generate equations from routinely measured clinic and blood variables for predicting clamp-derived glucose disposal rate (GDR), i.e., insulin sensitivity. We assembled data from hyperinsulinemic-euglycemic clamps (120 mU/m(2)·min insulin dose) performed at the Pennington Biomedical Research Center between 2001 and 2011. Subjects were divided into subjects with diabetes (n = 51) and subjects without diabetes (n = 116) by self-report and/or fasting glucose ≥126 mg/dL. We found that 75% of individuals with a GDR <5.6 mg/kg fat-free mass (FFM) + 17.7·min were truly insulin resistant. Cutoff values for GDRs normalized for body weight, body surface area, or FFM were 4.9 mg/kg·min, 212.2 mg/m(2)·min, and 7.3 mg/kgFFM·min, respectively. Next, we used classification tree models to predict GDR from routinely measured clinical and biochemical variables. We found that individual insulin resistance could be estimated with good sensitivity (89%) and specificity (67%) from the homeostasis model assessment of insulin resistance (HOMA-IR) >5.9 or 2.8< HOMA-IR <5.9 with HDL <51 mg/dL. We developed a cutoff for defining insulin resistance from hyperinsulinemic-euglycemic clamps. Moreover, we now provide classification trees for predicting insulin resistance from routinely measured clinical and biochemical markers. These findings extend the clamp from a research tool to providing a clinically meaningful message for participants in research studies, potentially providing greater opportunity for earlier recognition of insulin resistance.

Background: Metabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured. Methodology and Principal Findings: Forty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m2) participants were randomized to four groups for 6-months; Control: energy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were −1.0+/-1.1% (Control), −10.4+/-0.9% (CR), −10.0+/-0.8% (CR+EX) and −13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (−454+/-76 kcal/d) and LCD (−633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (−316+/-118 kcal/d) and LCD (−389+/-124 kcal/d) but reached significance only when CR and LCD were combined (−351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by −431+/-51 and −240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6. Conclusions: For the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance. Trial Registration: ClinicalTrials.gov NCT00099151.

Caloric restriction (CR) can enhance human health, though underlying mechanisms, particularly related to energy expenditure, remain unclear. This ancillary investigation of the only randomized controlled trial of long-term CR in normal-weight adults, aimed to quantify metabolic adaptation following weight loss by assessing changes in energy-expending tissues and organs using magnetic resonance imaging (MRI). Participants in the CR group were prescribed 24-month 25% CR causing a ~ 13% weight loss at 12 months followed by 12 month weight maintenance, whereas the control group maintained ad libitum food intake throughout. The CR group experienced reductions in adipose tissue and skeletal muscle mass compared to the control group. Sleeping energy expenditure decreased more than predicted at 12 months, regardless of whether predictions were based on body mass, dual x-ray absorptiometry (DXA)-derived body composition, or MRI-derived tissue mass. MRI-derived models explained slightly more variation in energy expenditure at baseline and detected greater metabolic adaptation than simpler models based on body mass only. At 24 months, only the models based on DXA and MRI were indicative of persistent metabolic adaptation. These findings highlight the complexity of metabolic responses to CR. Further, advanced imaging techniques hold potential to provide insight into organ-specific contributions to energy metabolism during CR.

Natural disasters can lead to more adverse pregnancy outcomes (APO). It is unclear if the extended COVID-19 pandemic has impacted APOs and pre-existing conditions among perinatal populations with increased risk of severe maternal morbidity and mortality. A retrospective chart review was conducted of hospital records and birth certificates in the largest birth hospital in Louisiana from 2017 to 2022. Amongst 27,877 births (50.9% White, 38.3% Black, 28.9 ± 5.6 years), gestational diabetes (GDM) was lowest in pre-pandemic conceptions (11.0%, June 2017-May 2019) and rose to 16.4% early pandemic (October 2019-February 2020) but leveled off at 12.2% in peak (March 2020-February 2021) and late pandemic (March 2021-September 2021). Individuals who conceived in early and peak pandemic were 47% (95% CI 33, 63) and 11% (95% CI 2, 20) more likely to develop GDM respectively, compared to pre-pandemic conceptions. Individuals who delivered during early (aRR: 1.54, 95% CI 1.33–1.78), peak (aRR: 1.48, 95% CI 1.32–1.65), and late (aRR: 1.62, 95% CI 1.41, 1.85) pandemic were more likely to develop preeclampsia and HELLP syndrome compared to pre-pandemic conceptions. Individuals were also 17% (95% CI 5, 32) more likely to enter pregnancy with chronic hypertension in peak pandemic compared to pre-pandemic. In paired analysis ( n  = 3390), individuals with a pandemic conception that occurred early pandemic had a higher risk of developing GDM compared to their pre-pandemic pregnancy (aOR 3.26, 95% CI 1.52, 6.97). Supporting birthing individuals amongst significant stressful events, especially in early gestation, is critical for preventing APOs and severe maternal morbidity and mortality.

Background It is unclear how physical activity energy expenditure (PAEE) influences calorie restriction (CR)-induced benefits in individuals without obesity. We examined associations between PAEE and healthspan markers and physical activity (PA) time during prolonged CR. Methods In Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)™ 2, participants without obesity were randomized to 25% CR or ad libitum control. This post-hoc analysis included baseline and 24-month data from participants in both groups who demonstrated CR. PAEE was calculated from total and resting energy expenditure, measured using doubly labelled water and indirect calorimetry, respectively, and adjusted for covariates to obtain a residual value that was used as the primary exposure variable. Outcomes included grip strength, aerobic capacity, glucose, insulin, blood lipids, and self-reported PA time. Results Overall, 136 participants (97 [71.3%] females; age: 38.6 [7.4] years; BMI: 25.3 [1.7] kg/m²) who showed CR were analyzed. A smaller decrease in PAEE was associated with improved grip strength (estimate = 0.504 [95% CI: 0.023, 0.986] kg), homeostatic model assessment of insulin resistance (estimate: -0.032 [95% CI: -0.062, -0.002]), and high-density lipoprotein-cholesterol (1.011 [95% CI: 0.356, 1.666] mg/dL; P  ≤ 0.040). PAEE change was not associated with aerobic capacity, low-density lipoprotein-cholesterol, triglycerides, glucose, or insulin ( P  ≥ 0.053). A smaller PAEE decline was associated with more PA minutes ( P  = 0.028). For some blood lipids, change in PAEE interacted with baseline BMI class ( P  ≤ 0.029): in participants who were overweight, higher PAEE was associated with lower triglyceride and triglyceride: high-density lipoprotein-cholesterol ratio ( P  ≤ 0.022), whereas in participants who were normal weight, it was related to increased total-cholesterol ( P  = 0.006). Conclusion A smaller reduction in PAEE during CR was associated with small improvements in several healthspan markers and greater PA time. Maintaining PAEE during CR may enhance healthspan in individuals without obesity. Trial registration clinicaltrials.gov registration (NCT00427193).

According to the Social Ecological Model of Behavior Change, support persons and the immediate household environment are crucial pillars of behavior change. In the context of pregnancy, we hypothesize that promotion of effective behavior changes to support healthy GWG depends on individual-level factors, in addition to support and adoption of health behavior change in partners, and couple-determined changes to the overall household environment (Fig. 1). [...]their statement that partners encouraged pregnant women to overeat and that some women reported their partners as a ‘feeder’ suggests partners have their own view of eating behavior that might change during pregnancy. [...]the authors described that some women reported relying on family and friends for advice on healthful diets and physical activity; yet this advice was sometimes discordant with their own beliefs.

The effects of female sex hormones on optimal performance have been increasingly recognized as an important consideration in exercise and sport science research. This narrative review explores the findings of studies evaluating the effects of menstrual cycle phase in eumenorrheic women and the use of hormonal contraception (oral contraceptives and hormonal intrauterine devices) on metabolism, muscular strength, and recovery in active females. Ovarian hormones are known to influence metabolism because estrogen is a master regulator of bioenergetics. Importantly, the menstrual cycle may impact protein synthesis, impacting skeletal muscle quality and strength. Studies investigating muscular strength in eumenorrheic women report equivocal findings between the follicular phase and luteal phase with no differences compared to oral contraceptive users. Studies examining recovery measures (using biomarkers, blood lactate, and blood flow) do not report clear or consistent effects of the impact of the menstrual cycle or hormonal contraception use on recovery. Overall, the current literature may be limited by the evaluation of only one menstrual cycle and the use of group means for statistical significance. Hence, to optimize training and performance in females, regardless of hormonal contraception use, there is a need for future research to quantify the intra-individual impact of the menstrual cycle phases and hormonal contraceptive use in active females.

Background Postpartum weight retention is a major contributor to obesity in later life resulting in long‐term health consequences in women. Postpartum lifestyle interventions are known to be effective in reducing postpartum weight retention and improving the overall health and wellbeing of mothers but have poor reach and engagement. This study describes the engagement of mothers with young children in the development of a theory‐ and evidence‐based intervention to reduce postpartum weight retention. Methods A participatory design methodology with input from a community mothers' group, literature reviews and an expert advisory group was applied. Mothers who were members of ‘Mothers of Preschoolers’ (MOPS) were invited to participate in a focus group discussion and two co‐design workshop sessions. Results Thirteen women participated in a focus group discussion and 12 women in each co‐design workshop. We found that mothers valued having social support from their peers, practical support such as meal delivery, and learning opportunities that focus on the mother's health and wellbeing. The advisory group suggested leveraging the unique skills and prior experiences of mothers within the group and developing a curriculum that mothers can be trained to deliver. Conclusion A program that emphasizes the strengths and value of mothers can increase their self‐worth and self‐confidence resulting in intrinsic motivation to improve lifestyle behaviours. An intervention designed to be implemented by MOPS for its members and incorporated into their regular sessions has the potential for feasibility and acceptability among mothers with young children. Patient or Public Contribution Mothers with young children were part of the program planners and were involved in the design and conduct of this study and in the interpretation of the findings. A member of a community mothers' group recruited other mothers with young children within the group to participate in a series of sessions to discuss their experiences of the postpartum period and preferences for a lifestyle program. The mothers identified the behavioural outcomes and program goals for a postpartum lifestyle program and then generated the program ideas based on these.

Background Mobile technology is ubiquitous. Women of childbearing age have embraced health information technology for pregnancy-related counsel as prenatal care provider communication is increasingly scarce and brief. Pregnant women and new mothers place high value in the use of online sources to support their pregnancy information needs. In Canada, over 300,000 women are pregnant annually, with approximately 60% exceeding evidence-based weight gain recommendations. Mobile health (mHealth) tools, such as mobile applications (app), have the potential to reduce excessive gestational weight gain, offering pregnant women trustworthy guidance, ultimately improving the health outcomes of mothers and infants. Therefore, the primary aim of this study was to implement a qualitative, descriptive research design to assess the receptiveness, functionality, and future prospective of the SmartMoms Canada mHealth app. Methods Two focus groups ( n  = 13) involving both currently pregnant and recently postpartum women were organized on the same day. Focus groups were transcribed verbatim and thematic analysis was undertaken using manual coding and NVivo software. Participants who took part in the focus groups (n = 13) and those who could not attend ( n  = 4) were asked to complete a Likert-scale survey. All survey responses ( n  = 17) were analyzed using simple tabulation and percentage analysis. Results Participants were technologically proficient and interacted with several mHealth tools prior to testing the SmartMoms Canada app. Six major themes emerged from thematic analysis: knowledge of pregnancy-specific mHealth services, knowledge and attitudes of weight gain guidelines, weight tracking, strengths of the app, critique and lastly, future suggestions for the app. Conclusions Our thematic analysis found that women positively viewed the future potential of our app and offered constructive feedback to improve the next version. Participants sought more personalization and enhanced app interactivity, along with promotion of overall maternal health including nutrition and mental health, in addition to weight tracking.