Changes In Energy Expenditure Research Articles

Crosstalk between Drp1 phosphorylation sites during mitochondrial remodeling and their impact on metabolic adaptation

SummaryMitochondria constantly undergo fusion and fission events, referred as mitochondrial dynamics, which determine mitochondrial architecture and bioenergetics. Cultured cell studies demonstrate that mitochondrial dynamics are acutely regulated by phosphorylation of the mitochondrial fission orchestrator dynamin-related protein 1 (Drp1) at S579 or S600. However, the physiological impact and crosstalk of these phosphorylation sites is poorly understood. Here, we describe the functional interrelation between S579 and S600 phosphorylation sites in vivo and their role on mitochondrial remodeling. Mice carrying a homozygous Drp1 S600A knockin (Drp1 KI) mutation display larger mitochondria and enhanced lipid oxidation and respiratory capacities, granting improved glucose tolerance and thermogenic response upon high-fat feeding. Housing mice at thermoneutrality blunts these differences, suggesting a role for the brown adipose tissue in the protection of Drp1 KI mice against metabolic damage. Overall, we demonstrate crosstalk between Drp1 phosphorylation sites and provide evidence that their modulation could be used in the treatment and prevention of metabolic diseases.

Changes in daily energy expenditure and movement behavior in unilateral vestibular hypofunction: Relationships with neuro-otological parameters

The vestibular system has been found to affect energy homeostasis and body composition, due to its extensive connections to the brainstem and melanocortin nuclei involved in regulating the metabolism and feeding behavior. The aim of this study was to evaluate – by means of a wrist-worn physical activity tracker and bioelectrical impedance analysis (BIA) – the energy expenditure (EE) in resting (REE) and free-living conditions and movement behavior in a group of chronic unilateral vestibular hypofunction (UVH) patients when compared with a control group (CG) of healthy participants. Forty-six chronic UVH and 60 CG participants underwent otoneurological (including video-Head Impulse Test [vHIT] for studying vestibulo-ocular reflex [VOR] and static posturography testing [SPT]), and EE and movement measurements and self–report (SRM) andperformance measures (PM). As well as significant (p < 0.001) changes in SPT variables (area and path length) and SRM/PM, UVH participants also demonstrated significantly (p < 0.001) lower values in REE, movement EE, hours/day spent upright, number of strides and distance covered and total daily EE (p = 0.007) compared to the CG. UVH patients consumed significantly lower Kcal/min in sweeping (p = 0.001) and walking upstairs and downstairs (p < 0.001) compared to the CG. Multiple correlations were found between free-living and resting EE and neuro-otological parameters in UVH participants. Since the melanocortin system could be affected along the central vestibular pathways as a consequence of chronic vestibular deafferentation, data collected by reliable wearables could reflect the phenomena that constitute an increased risk of falls and sedentary lifestyle for patients affected by UVH, and could improve rehabilitation stages.

Can resveratrol modulate sirtuins in obesity and related diseases? A systematic review of randomized controlled trials.

Human sirtuins can be a powerful therapeutic target in preventing and treating obesity and age-related diseases. Some dietary components can modulate sirtuins' activity, such as resveratrol. This systematic review aimed to assess whether resveratrol (RSV), without other interventions, can stimulate sirtuins in the treatment of excess weight and its comorbidities. MEDLINE/Pubmed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were used for search eligible articles. Randomized clinical trials assessing RSV supplementation on changes in the sirtuins' gene expression/protein levels was the primary outcome. Other possible changes in cardiometabolic markers were consideredthe second outcome. Following PRISMA guidelines and using predefined inclusion and exclusion criteria, two reviewers independently and in parallel screened, assessed the studies' quality, and compiled data. Disagreements were resolved by consensus or consulting a third author. This review included seven randomized control trials. Four articles demonstrated a significant increase in SIRT-1 with different RSV dosages and interventions time. The secondary outcomes showed improvements in insulin sensitivity, lipid profile, metabolic flexibility, total antioxidant capacity, energy expenditure changes, and reduction of ectopic accumulation of fat. Data from RCTs studies showed that RSV supplementation could stimulate SIRT-1 in humans, and therefore contribute to the treatment of excess weight and its comorbidities. However, more research is needed because it was not possible to confirm this effect truly. [PROSPERO registration number: CRD42020205571].

Sex differences and shifts in body composition, physical activity, and total energy expenditure across a 3-month expedition.

An energetically demanding environment like a wilderness expedition can lead to potent stressors on human physiology and homeostatic balance causing shifts in energy expenditure and body composition. These shifts likely have consequences on overall health and performance and may potentially differ by sex. It is therefore critical to understand the potential differential body composition and energy expenditure changes in response to a novel and challenging environment in both males and female bodies. Data were collected from 75 healthy individuals (female=41; ages 18-53) throughout a 3-month long expedition in the American Rockies. Body mass, body fat, and lean muscle mass were measured before, during, and after the course. Physical activity intensity and energy expenditure were also measured in a subset of participants using the wGT3X-BT Actigraph wrist monitor and an accompanying Bluetooth heart rate monitor. Over the 3-month period, individuals initially experienced declines in body mass, body fat percentage, and lean muscle mass. Participants partially rebounded from these deficits to maintain overall body mass with a slight recomposition of body fat and lean muscle mass. Our data also demonstrated that sex moderated total energy expenditure, where females experienced a modest decline whereas males experienced an increase in energy expenditure from the beginning to the end of the course. Understanding changes in energy storage in the body and variation in energy expenditure between sexes during a 3-month expedition has critical implications for maintaining health and performance in an energetically demanding environment where resources may be scarce.

682-P: Novel Dual Glucagon and Glucagon-Like Peptide-1 Receptor Agonist LY3305677 Improves Glucose Control, Reduces Body Weight, and Increases Energy Expenditure in Mice

LY3305677 (LY) is a synthetic peptide analog of mammalian oxyntomodulin with a fatty acyl side chain to extend time action. LY functions are mediated by binding and activation of both glucagon (GcgR) and glucagon-like peptide-1 (GLP-1R) receptors. LY is bound with potent binding affinity (Ki) to human and mouse GcgR (Ki: 17.7 nM and 15.9 nM, respectively) and GLP-1R (Ki: 28.6 nM and 25.1 nM, respectively). LY dose-dependently stimulated insulin secretion in mouse pancreatic islets (EC50: 5.2 nM) and in mice. In oral glucose tolerance tests of diet-induced obese (DIO) and streptozotocin-induced diabetic mice, a single subcutaneous (SC) dose of LY significantly reduced glucose area under the curve by up to 65%. SC injections of LY to DIO mice dose-dependently reduced serum triglycerides and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels and dose-dependently increased FGF21 (fibroblast growth factor 21) levels. In DIO mice treated over 18 days, LY 30 nmol/kg reduced body weight to a greater extent (33%) than semaglutide 60 nmol/kg (12%), and decreased food intake by 50% compared to vehicle. At Day 18, LY 30 nmol/kg group lost 33% of initial bodyweight, which was primarily due to 70% reduced fat mass. LY reduced liver triglycerides by greater than 70% and increased serum ketones by more than 3-fold compared to vehicle, suggestive of increased fatty acid oxidation. LY decreased body weight in both GcgR knock-out (KO) and GLP-1R KO mice, indicating that activation of both receptors contributed to greater weight loss. To assess potential changes in energy expenditure, DIO mice were treated chronically with SC LY (15 nmol/kg), semaglutide (60 nmol/kg), or vehicle. LY, but not semaglutide, increased energy expenditure as compared with vehicle. These preclinical studies indicate that novel dual GcgR and GLP-1R agonist LY may have potential to enhance metabolic health by improving dyslipidemia, hyperglycemia, or obesity. Disclosure Y. Chen: None. H. Qu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. A. Mezo: None. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Song: None. W. C. Roell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. B. Bokvist: Employee; Self; Eli Lilly and Company, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Self; Johnson &amp; Johnson, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J. S. Moyers: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. F. Valenzuela: None. Funding Eli Lilly and Company

105-OR: An Exploratory Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Cotadutide on Energy Balance in Overweight and Obese Subjects with Type 2 Diabetes Mellitus

Background: Cotadutide is a GLP1/glucagon receptor dual agonist under development for the treatment of nonalcoholic steatohepatitis and type 2 diabetes (T2D) with diabetic kidney disease. Early-phase clinical studies show that cotadutide achieves clinically significant weight loss. We aimed to establish mechanistically to what extent this effect is mediated via changes in energy intake (EI) or energy expenditure (EE). Methods: We conducted a phase 2a single-center randomized double-blind placebo-controlled trial in overweight/obese adults (BMI 27-40 kg/m2) with T2D (HbA1c 6.5-8%). Participants underwent a 16-day single-blind placebo run-in and were randomized to double-blind 42-day cotadutide or placebo. Cotadutide was given subcutaneously, up to 300 µg daily. Primary outcome: % weight change from day 17 to day 59. Secondary outcomes: % and absolute changes in EI (ad libitum lunch), and EE (indirect calorimetry). Results: A total of 19 (63%) cotadutide and 9 (78%) placebo participants completed the study. Least-squares (LS) mean weight change was -3.98% (90% CI -4.85%, -3.10%) and -1.40% (90% CI -2.66%, -0.13%) for cotadutide and placebo, respectively, p= 0.011 between groups. The cotadutide group had a striking 35% lower EI vs. placebo: LS mean -35.0% (90% CI -61.8%, -8.2%), p=0.037. Total EE (kJ/kg lean mass) after cotadutide treatment decreased vs. placebo: -6.0% vs. 0.3%, p&amp;lt;0.001. Significant reductions in absolute resting and activity EE were noted with cotadutide after 42 days, but there was no change in resting EE (8.5%; cotadutide vs. placebo 1.2%, p=0.177) after 16 days of therapy despite a reduction in body weight. No additional safety concerns were raised. Conclusions: Weight loss caused by cotadutide is predominantly due to reduced EI rather than increased EE. Transient preservation of EE in the early phases of cotadutide treatment may reflect glucagon receptor engagement. Disclosure R. Golubic: None. M. Evans: Advisory Panel; Self; Pila Pharma, Zucara Therapeutics Inc., Other Relationship; Self; Abbott Diabetes, Medtronic, Novo Nordisk, Research Support; Self; AstraZeneca, Imcyse. J. Kennet: None. V. E. Parker: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. D. Robertson: Employee; Self; AstraZeneca, Employee; Spouse/Partner; GlaxoSmithKline plc., Stock/Shareholder; Self; AstraZeneca. D. Luo: None. L. Hansen: Employee; Self; AstraZeneca. L. Jermutus: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; AstraZeneca. A. Park: Other Relationship; Self; Novo Nordisk.

Dirençli Egzersiz Eğitiminin Obez Bireylerde Vücut Kas ve Yağ Parametreleri Üzerine Etkisi

Obesity is a multifactorial disease with an increasing prevalence worldwide and is characterized by an increase in body weight. It poses a risk for diseases such as hypertension and diabetes, especially by causing an increase in fat in the abdominal area. Obesity can be managed through behavioral changes in energy intake or expenditure. Various nutrition and exercise strategies are used for this purpose. Exercise causes an increase in energy expenditure and contributes to a decrease in body weight, loss of fat mass and the maintenance of these effects. Exercise has the potential to mitigate the adverse health consequences of obesity even without weight loss in the body. Studies suggest that resistance exercise training can promote a negative energy balance, play a role in weight management by changing body fat mass. Increase in muscle mass with resistance exercise training provides a better metabolic control in the body. From the perspective of weight loss and control, recent exercise guidelines include resistance exercise training as part of an exercise prescription. Resistance exercise training can play an important role in body fat management, with an increase in energy expended during physical activity and an acute increase in basal metabolic rate. Resistance exercise training can increase lean body mass and cause changes in body composition by reducing visceral and total body fat. However, the effects of resistance exercise training on body fat composition still do not give definitive results. In this respect, this review aims to examine the effects of resistance exercise training on body fat mass and muscle.

Sleep Quality and Physical Activity as Predictors of Mental Wellbeing Variance in Older Adults during COVID-19 Lockdown: ECLB COVID-19 International Online Survey.

Background. The COVID-19 lockdown could engender disruption to lifestyle behaviors, thus impairing mental wellbeing in the general population. This study investigated whether sociodemographic variables, changes in physical activity, and sleep quality from pre- to during lockdown were predictors of change in mental wellbeing in quarantined older adults. Methods. A 12-week international online survey was launched in 14 languages on 6 April 2020. Forty-one research institutions from Europe, Western-Asia, North-Africa, and the Americas, promoted the survey. The survey was presented in a differential format with questions related to responses “pre” and “during” the lockdown period. Participants responded to the Short Warwick–Edinburgh Mental Wellbeing Scale, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and the short form of the International Physical Activity Questionnaire. Results. Replies from older adults (aged >55 years, n = 517), mainly from Europe (50.1%), Western-Asia (6.8%), America (30%), and North-Africa (9.3%) were analyzed. The COVID-19 lockdown led to significantly decreased mental wellbeing, sleep quality, and total physical activity energy expenditure levels (all p < 0.001). Regression analysis showed that the change in total PSQI score and total physical activity energy expenditure (F(2, 514) = 66.41 p < 0.001) were significant predictors of the decrease in mental wellbeing from pre- to during lockdown (p < 0.001, R2: 0.20). Conclusion. COVID-19 lockdown deleteriously affected physical activity and sleep patterns. Furthermore, change in the total PSQI score and total physical activity energy expenditure were significant predictors for the decrease in mental wellbeing.

Changes in Body Composition, Energy Expenditure, and Energy Intake during Four Years of University-A Follow-Up Study.

Purpose: The transition to university is often accompanied by the adoption of negative lifestyle habits, which may result in weight and fat gain. While this has been demonstrated during 1st year, little is known about subsequent years. We investigated changes in body composition, energy expenditure, and dietary/energy intake from 1st to 4th year university. Methods: Thirty-eight students (14 males, 24 females) completed a lifestyle questionnaire and had their body mass, fat mass, lean body mass (LBM), and body fat percentage (%BF) measured three times: at the beginning and end of 1st year, and end of 4th year. Results: During 1st year, body mass, fat mass, LBM, and %BF increased (+3.2 ± 3.8 kg, +2.5 ± 3.0 kg, +0.7 ± 2.1 kg, +2.3 ± 4.9%, respectively; p < 0.01), while daily energy intake and expenditure decreased (−359 ± 1019 kcal·d−1 and −434 ± 786 kcal·d−1, respectively; p < 0.01). Between the end of 1st year and end of 4th year, body mass, LBM, and energy expenditure increased (+3.2 ± 3.8 kg, +1.3 ± 2.9 kg, +209 ± 703 kcal·d−1, respectively; p ≤ 0.05), while %BF, fat mass, and energy intake did not change. Conclusions: Although %BF and fat mass remained stable from the end of 1st year to the end of 4th year in this group of university students, the positive increase in energy expenditure was not enough to reverse the weight and fat gained during 1st year.

Photoperiod Manipulation Reveals a Light-Driven Component to Daily Patterns of Ventilation in Male C57Bl/6J Mice.

Obstructive sleep apnea is a common sleep disorder that increases risk for cardiovascular disease and mortality. The severity of sleep-disordered breathing in obstructive sleep apnea patients fluctuates with the seasons, opening the possibility that seasonal changes in light duration, or photoperiod, can influence mechanisms of breathing. Photoperiod can have profound effects on internal timekeeping and can reshape metabolic rhythms in mammals. While the daily rhythm in ventilation is largely shaped by the metabolic rate, less is known about whether ventilatory rhythms are altered in accordance with metabolism under different photoperiods. Here, we investigate the relationship between ventilation and metabolism under different photoperiods using whole-body plethysmography and indirect calorimetry. We find that the daily timing of ventilation is chiefly synchronized to dark onset and that light cues are important for maintaining daily ventilatory rhythms. Moreover, changes in ventilatory patterns are not paralleled by changes in oxygen consumption, energy expenditure, or respiratory exchange rate under different photoperiods. We conclude that ventilatory patterns are not only shaped by the metabolic rate and circadian timing but are also influenced by other light-driven factors. Collectively, these findings have clinical implications for the seasonal variations in sleep-disordered breathing found in individuals with obstructive sleep apnea.

Childhood Daily Energy Expenditure Does Not Decrease with Market Integration and Is Not Related to Adiposity in Amazonia

BackgroundChildhood overweight and obesity (OW/OB) is increasingly centered in low- and middle-income countries (LMICs) as rural populations experience market integration and lifeway change. Most explanatory studies have relied on imprecise estimates of children’s energy expenditure, restricting understanding of the relative effects of changes in diet and energy expenditure on the development of OW/OB in transitioning contexts. ObjectivesThis study used gold-standard measurements of children’s energy expenditure to investigate the changes that underlie OW/OB and the nutrition/epidemiologic transition. MethodsCross-sectional data were collected from “rural” (n = 43) Shuar forager-horticulturalist children and their “peri-urban” (n = 34) Shuar counterparts (age 4–12 y) in Amazonian Ecuador. Doubly labeled water measurements of total energy expenditure (TEE; kcal/d), respirometry measurements of resting energy expenditure (REE; kcal/d), and measures of diet, physical activity, immune activity, and market integration were analyzed primarily using regression models. ResultsPeri-urban children had higher body fat percentage (+8.1%, P < 0.001), greater consumption of market-acquired foods (multiple P < 0.001), lower concentrations of immune activity biomarkers (multiple P < 0.05), and lower REE (−108 kcal/d, P = 0.002) than rural children. Despite these differences, peri-urban children’s TEE was indistinguishable from that of rural children (P = 0.499). Moreover, although sample-wide IgG concentrations and household incomes predicted REE (both P < 0.05), no examined household, immune activity, or physical activity measures were related to children’s overall TEE (all P > 0.09). Diet and energy expenditure associations with adiposity demonstrate that only reported consumption of market-acquired “protein” and “carbohydrate” foods predicted children’s body fat levels (multiple P < 0.05). ConclusionsDespite underlying patterns in REE, Shuar children’s TEE is not reliably related to market integration and—unlike dietary measures—does not predict adiposity. These findings suggest a leading role of changing dietary intake in transitions to OW/OB in LMICs.

Growth hormone receptor in dopaminergic neurones regulates stress-induced prolactin release in male mice.

Arcuate nucleus (ARH) dopaminergic neurones regulate several biological functions, including prolactin secretion and metabolism. These cells are responsive to growth hormone (GH), although it is still unknown whether GH action on ARH dopaminergic neurones is required to regulate different physiological aspects. Mice carrying specific deletion of GH receptor (GHR) in tyrosine hydroxylase (TH)- or dopamine transporter (DAT)-expressing cells were produced. We investigated possible changes in energy balance, glucose homeostasis, fertility, pup survival and restraint stress-induced prolactin release. GHR deletion in DAT- or TH-expressing cells did not cause changes in food intake, energy expenditure, ambulatory activity, nutrient oxidation, glucose tolerance, insulin sensitivity and counter-regulatory response to hypoglycaemia in male and female mice. In addition, GHR deletion in dopaminergic cells caused no gross effects on reproduction and pup survival. However, restraint stress-induced prolactin release was significantly impaired in DAT- and TH-specific GHR knockout male mice, as well as in pegvisomant-treated wild-type males, whereas an intact response was observed in females. Patch clamp recordings were performed in ARH DAT neurones and, in contrast to prolactin, GH did not cause acute changes in the electrical activity of DAT neurones. Furthermore, TH phosphorylation at Ser40 in ARH neurones and median eminence axonal terminals was not altered in DAT-specific GHR knockout male mice during restraint stress. In conclusion, GH action in dopaminergic neurones is required for stress-induced prolactin release in male mice, suggesting the existence of sex differences in the capacity of GHR signalling to affect prolactin secretion. The mechanism behind this regulation still needs to be identified.

Stretch-Shortening Cycle Potentiation and Resistance Training-Induced Changes in Walking Economy/Ease and Activity-Related Energy Expenditure in Older Women.

Hunter, GR, Singh, H, Martins, C, Baranauskas, MN, and Carter, SJ. Stretch-shortening cycle potentiation and resistance training-induced changes in walking economy/ease and activity-related energy expenditure in older women. J Strength Cond Res 35(5): 1345-1349, 2021-Use of elastic energy to improve economy and ease of walking may be important for older adults. The purpose of this investigation was to determine whether baseline (i.e., untrained) stretch-shortening cycle potentiation (SSCP) was associated with potential changes in free-living activity-related energy expenditure (AEE) after supervised exercise training. Sedentary, postmenopausal women (n = 64) between 60 and 74 years of age were evaluated before and after 16 weeks of combined aerobic and resistance training. Assessments included: (a) body composition (dual-energy X-ray absorptiometry), (b) resting energy expenditure (indirect calorimetry), (c) submaximal and maximal walking (treadmill/indirect calorimetry), (d) total energy expenditure (doubly labeled water), and (e) one repetition maximum performed on an incline leg press and SSCP (calculated as the difference between concentric and countermovement leg press throw). Results indicated that baseline SSCP was related (r = -0.29; p < 0.02) to changes in AEE. However, subjects who possessed a high baseline SSCP did not increase SSCP or AEE, whereas subjects with low to moderate baseline SSCP demonstrated a significant increase in both SSCP (low +0.54 and moderate +0.47 m·s-1) and AEE (low +158 and moderate +333 kcal·d-1) post-training (all p less than 0.05). Our findings suggest that among subjects with low to moderate baseline SSCP, 16 weeks of combined aerobic and resistance training can increase SSCP and free-living AEE. However, subjects with high baseline SSCP may require tailored exercise to increase SSCP and possibly AEE.

Effectiveness of Minimal Contact Interventions: An RCT

IntroductionAround 23% of adults worldwide are insufficiently active. Wearable devices paired with virtual coaching software could increase physical activity. The effectiveness of 3 minimal contact interventions (paper-based physical activity diaries, activity trackers, and activity trackers coupled with virtual coaching) in increasing physical activity energy expenditure and cardiorespiratory fitness were compared over 12 weeks among inactive adults.MethodsThis was an open label, parallel-group RCT. Inactive adults (aged ≥18 years, N=488) were randomized to no intervention (Control; n=121), paper-based diary (Diary; n=124), activity tracker (Activity Band; n=122), or activity tracker plus virtual coaching (Activity Band PLUS; n=121) groups. Coprimary outcomes included 12-week changes in physical activity energy expenditure and fitness (May 2012–January 2014). Analyses were conducted in 2019–2020.ResultsThere were no differences between groups overall (physical activity energy expenditure: p=0.114, fitness: p=0.417). However, there was a greater increase in physical activity energy expenditure (4.21 kJ/kg/day, 95% CI=0.42, 8.00) in the Activity Band PLUS group than in the Diary group. There were also greater decreases in BMI and body fat percentage in the Activity Band PLUS group than in the Control group (BMI= −0.24 kg/m2, 95% CI= −0.45, −0.03; body fat= −0.48%, 95% CI= −0.88, −0.08) and in theActivity Band PLUS group than in the Diary group (BMI= −0.30 kg/m2, 95% CI= −0.50, −0.09; body fat= −0.57%, 95% CI= −0.97, −0.17).ConclusionsCoupling activity trackers with virtual coaching may facilitate increases in physical activity energy expenditure compared with a traditional paper‒based physical activity diary intervention and improve some secondary outcomes compared with a traditional paper‒based physical activity diary intervention or no intervention.Trial registrationThis study is registered at www.clinicaltrials.gov ISRCTN31844443.

Genetic ablation of C-reactive protein gene confers resistance to obesity and insulin resistance in rats.

Besides serving as a traditional inflammatory marker, C-reactive protein (CRP) is closely associated with the development of obesity, diabetes and cardiovascular diseases as a metabolic and inflammatory marker. We hypothesise that CRP protein directly participates in the regulation of energy and glucose metabolism rather than just being a surrogate marker, and that genetic deficiency of CRP will lead to resistance to obesity and insulin resistance. Crp gene deletion was achieved by transcription activator-like effector nuclease (TALEN) technology in rats. The Crp knockout animals were placed on either a standard chow diet or a high-fat diet. Phenotypic changes in body weight, glucose metabolism, insulin sensitivity, energy expenditure and inflammation condition were examined. The central impact of CRP deficiency on leptin and insulin hypothalamic signalling, as well as glucose homeostasis, were examined via intracerebral ventricular delivery of leptin and CRP plus glucose clamp studies in the wild-type and Crp knockout rats. CRP deficiency led to a significant reduction in weight gain and food intake, elevated energy expenditure and improved insulin sensitivity after exposure to high-fat diet. Glucose clamp studies revealed enhanced hepatic insulin signalling and actions. Deficiency of CRP enhanced and prolonged the weight-reducing effect of central injected leptin and promoted the central and peripheral roles of leptin. By contrast, reinstatement of CRP into the hypothalamus of the knockout rats attenuated the effects of central leptin signalling on insulin sensitivity and peripheral glucose metabolism. This study represents the first line of genetic evidence that CRP is not merely a surrogate blood marker for inflammation and metabolic syndromes but directly regulates energy balance, body weight, insulin sensitivity and glucose homeostasis through direct regulation of leptin's central effect and hypothalamic signalling.

EXCESSIVE WEIGHT GAIN IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS ON ANTI-TNF THERAPY

Abstract Background Limited studies in patients with inflammatory bowel disease (IBD) suggest that anti-TNF therapy may be associated with excessive weight gain. The objective of this study was to compare the change in BMI z-score in children with Crohn Disease (CD) on anti-TNF therapy (CD exposed) to those not on anti-TNF therapy (CD unexposed) over time. We also sought to determine if anti-TNF exposure is a risk factor for excessive weight gain and obesity. Methods This was a retrospective cohort study utilizing the RISK database, a longitudinal inception cohort of pediatric patients with CD. Multivariable logistic, linear random mixed effects, and multilevel mixed effects generalized linear regression models were used to evaluate the association of anti-TNF therapy with excessive weight gain, change in BMI z-score, and obesity, respectively. Excessive weight gain was defined as patients with a normal baseline BMI z-score who became overweight/obese or had a delta BMI z-score &amp;gt;1 at the end of follow-up, underweight patients who became overweight/obese, and overweight patients who became obese or had a delta BMI z-score &amp;gt;0.5 at the end of follow-up. Results 625 (61%) exposed and 404 (39%) unexposed patients were included. There was no difference in age at diagnosis or sex between groups, however the CD exposed group had lower BMI z-score [-0.9 (IQR -1.8, 0.0) vs -0.5 (IQR -1.4, 0.3)] as well as higher disease activity index [52.5 (IQR 35.0, 72.5) vs 40.0 (IQR 25, 57.5)] and C-reactive protein (CRP) [4.5 (IQR 1.4, 13.0) vs 2.7 (IQR 0.7, 9.0)] at baseline. 28% of the group exposed to anti-TNF therapy met criteria for excessive weight gain. Exposed patients were at 1.43 (CI 1.06, 1.93) greater odds of excessive weight gain as compared to the unexposed group, controlling for baseline BMI z-score and sex. BMI z-score increased with anti-TNF exposure, particularly in the first year of follow-up and in children who were underweight at baseline, controlling for baseline BMI z-score, sex, CRP, and steroid exposure (Table 1). Male sex was associated with higher BMI z-score, while CRP and steroid exposure were inversely related to BMI z-score. Exposed patients had increased adjusted odds of obesity and morbid obesity: OR 1.72 (CI 1.34, 2.20) and OR 5.72 (CI 2.77, 11.33), respectively (Table 2). Male sex and baseline BMI z-score also increased the odds of obesity and morbid obesity. Conclusion CD patients with anti-TNF exposure have a significant increase in BMI z-score over time as compared to patients unexposed to anti-TNF therapy. While for most patients this increase in BMI z-score is restorative, a subset of patients gain excessive weight or become obese. Anti-TNF therapy may be a risk-factor for this phenomenon. BMI z-score at diagnosis and male sex may also be risk factors. Future studies evaluating changes in adiposity and energy expenditure should be pursued. Note: Interaction term between anti-TNF and baseline BMI z-score. Interaction term between anti-TNF and time. Interaction term between anti-TNF and quadratic time. Note: Table for risk factors for morbid obesity in CD patients not included due to text constraints but with similar findings.

Proxy problems: Why a calibration is essential for interpreting quantified changes in energy expenditure from biologging data

Abstract We do not yet have the means to directly measure the energy expenditure of wild animals, particularly at a high temporal resolution. However, we can instead measure factors that correlate with energy expenditure, such as heart rate or accelerometry, that is, energy expenditure proxies. To estimate the magnitude of differences in energy expenditure between contexts (such as day and night, or travelling singly vs. in a group), our energy expenditure proxy must be calibrated. However, perhaps because of the logistical challenges of conducting such calibrations and the observation that most calibrations are linear, researchers sometimes interpret the degree of change in energy expenditure between contexts based on uncalibrated proxy data. When doing so, they implicitly assume that the ratio of the proxy values between contexts represents the ratio of energy expenditure values between those contexts. This approach, however, is usually spurious because unless the relationship between energy expenditure and proxy passes through the origin (i.e. y‐intercept = 0), the ratio of change in the proxy between contexts does not represent the ratio of change in energy expenditure. We model the error induced when data from an uncalibrated proxy are used to interpret changes in energy expenditure. We also estimate the errors made in published articles that employ this approach, by comparing the claimed change in energy expenditure between two contexts with the change in energy expenditure estimated by applying the best available calibrations now available. As predicted by the models we developed, the apparent size of the error in published articles is related to the relative size of the calibration y‐intercept. Species‐ and activity‐specific empirical calibrations are the best option for interpreting proxies of energy expenditure. However, for mammals and birds, enough data have been amassed such that energy expenditure can be predicted from measures of heart rate by knowing animal heart mass or even body mass; perhaps a somewhat analogous predictive tool will be available in the future for accelerometry. A free Plain Language Summary can be found within the Supporting Information of this article.

Self-weighing Practices and Associated Health Behaviors during COVID-19

Objective: In this study, we investigated self-weighing frequency (SWF) among adults during the COVID-19 pandemic and retrospectively (6 months) before the pandemic, and whether SWF was associated with changes in health-related behaviors. Methods: United States adults (N = 1607) completed a health-related questionnaire during COVID-19 and associated shelter-in-place. We categorized respondents into 4 groups of SWF at the time of the pandemic: "Never," "< 1x a week," "1x a week," or "> 1x a week." Results: The proportion of adults never weighing increased during the pandemic (15% to 25%), whereas the proportion of those weighing < 1x week went down (41% to 29%). Higher SWF was significantly associated with changes in energy expenditure including increased total physical activity (PA), lower likelihood of decreases in vigorous, moderate, and walking PA, and a lower likelihood of sitting more. More frequent self-weighing also was associated statistically with lower likelihood of keeping unhealthy eating behaviors the same. Conversely, there was no significant difference in changes in alcohol, caffeine, takeout, fruit or vegetable consumption, and television viewing among SWF groups. Conclusion: SWF decreased during the pandemic in the lower 2 SWF categories. Higher SWF was associated with fewer negative changes in health behaviors, especially related to PA.

Weight, Shape, and Body Composition Changes at Menopause.

Obesity and overweight are associated with increased risks of cardiovascular and metabolic disease and overall poor health outcomes. Menopause is associated with significant changes in body composition and the accumulation of peri-abdominal or visceral fat. Changes in energy expenditure and spontaneous activity have been noted. These mid-life changes can add further to the burden of obesity and its associated risks. An understanding of the role of estrogen, gonadotrophins, gut hormones, sleep deprivation and the microbiome is still rudimentary, but research will ultimately provide further targets for more effective management. This narrative review will explore the pathogenesis of body composition changes at menopause, the impact on health outcomes and therapeutic and management options.

Ontogenetic changes in energy expenditure and resting behaviour of humpback whale mother–calf pairs examined using unmanned aerial vehicles

Context Baleen whale calves rapidly increase in size and improve locomotion abilities, while on their low-latitude breeding ground, allowing them to undertake a successful migration to high-latitude feeding grounds. Aims We investigated energy expenditure and resting behaviour of humpback whale (Megaptera novaeangliae) mother–calf pairs in regard to changes in calf length on an undisturbed breeding/resting ground off Exmouth Gulf, Western Australia. Methods Data were collected from August to October in 2018 and 2019 on lactating mothers that were predominantly resting on the surface with their calf. Focal follows on mother–calf pairs (n = 101) were conducted using an unmanned aerial vehicle to obtain detailed video of behaviours and respirations (23.7 h). Body length measurements of individual whales were calculated from aerial still frames. Key results Results on calves ranging in length from ~4–8 m demonstrated that calf respiration rate decreased with an increase in calf length and increased with presence of activity (P &lt; 0.001). Calf inter-breath intervals became longer in duration with an increase in calf length (P &lt; 0.01). Calf activity level and resting behaviour remained constant, with calves logging for 53% of the time their mothers were logging. Maternal respiration rate remained low and did not differ with respect to maternal or calf length. Conclusions Results highlighted the importance of resting grounds for energy preservation, which benefits the calves’ rapid growth before migration to polar waters. Implications Findings from the present largely undisturbed population serve as a baseline for understanding the impacts of anthropogenic disturbance on resting behaviour and energy expenditure in humpback whale mother–calf pairs globally.