Energy Expenditure in Humans: Principles, Methods, and Changes Throughout the Life Course.

Humans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rate of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.

Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women.

Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5-12 and 20-25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, d rm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; d rm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; d rm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; d rm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.

Effects of ketone bodies on energy expenditure, substrate utilization, and energy intake in humans.

The potential of ketogenic approaches to regulate energy balance has recently gained attention since ketones may influence both energy expenditure and energy intake. In this narrative review, we summarized the most relevant evidence about the role of ketosis on energy expenditure, substrate utilization, and energy intake in humans. We considered different strategies to induce ketosis, such as fasting, dietary manipulation, and exogenous ketone sources. In general, ketosis does not have a major influence on energy expenditure but promotes a shift in substrate utilization towards ketone body oxidation. The strategies to induce ketosis by reduction of dietary carbohydrate availability (e.g., ketogenic diets) do not independently influence energy intake, being thus equally effective for weight loss as diets with higher carbohydrate content. In contrast, the intake of medium-chain triglycerides and ketone esters induces ketosis and appears to increase energy expenditure and reduce energy intake in the context of high carbohydrate availability. These latter strategies lead to slightly enhanced weight loss. Unfortunately, distinguishing the effects of the various ketogenic strategies per se from the effects of other physiological responses is not possible with the available human data. Highly controlled, inpatient studies using targeted strategies to isolate the independent effects of ketones are required to adequately address this knowledge gap.

Prevalence of non-alcoholic fatty liver disease and its association with lifestyle habits in adults in Chile: a cross-sectional study from the National Health Survey 2016-2017.

Non-alcoholic fatty liver disease (NAFLD) represents an excessive fat accumulation within the liver, usually associated with excess body weight. A liver biopsy is the gold standard for diagnosis, but it is inapplicable in population-based studies. In large populations, non-invasive methods could be used, which may also serve to identify potential protective factors. We aimed to (a) estimate NAFLD prevalence in the adult population in Chile by using non-invasive methods and (b) determine the association between the presence of NAFLD and lifestyle habits. The National Health Survey of Chile 2016­2017 was analysed. We included individuals aged 21­75 years, without infectious diseases nor risky alcohol consumption. NAFLD was detected by either fatty liver index (FLI; considers circulating TAG, circulating γ-glutamyl-transferase, BMI and waist circumference), lipid accumulation product (LAP; considers sex, circulating TAG and waist circumference) or their combination. Lifestyle habits were determined by questionnaires. We included 2774 participants, representative of 10 599 094 (9 831 644, 11 366 544) adults in Chile. NAFLD prevalence (95 % CI) was 39·4 % (36·2, 42·8) by FLI, 27·2 % (24·2, 30·4) by LAP and 23·5 % (20·7, 26·5) by their combination. The prevalence progressively increased with increasing BMI. Of note, less smoking and more moderate-vigorous physical activity and whole-grain consumption were associated with lower odds of having NAFLD, independently of BMI. At least one out of four adults in Chile is afflicted with NAFLD. Health promotion strategies focused on controlling excess body weight and promoting specific lifestyle habits are urgently required.

Low abundance of Mfn2 protein correlates with reduced mitochondria-SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images.

The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondria-sarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria-SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed "by-hand," thus potentially leading to between-rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial-SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial-SR juxtaposition, mitochondrial morphology, MCD (stereological-method), and SM quality (cross-sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2-HA; n = 6) and low abundance (Mfn2-LA; n = 6) of Mfn2 protein. The mitochondria-SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2-HA and Mfn2-LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2-LA group showed lower mitochondria-SR interaction, MCD, and VO2max . In conclusion, mitochondrial-SR juxtaposition measurement depends on the experience of the rater, and Mfn2 protein seems to play a role in the metabolic control of human men SM, by regulating the mitochondria-SR interaction.

[Physical inactivity versus sedentariness: analysis of the chilean national health survey 2016-2017]. / Inactividad física versus sedentarismo: análisis de la Encuesta Nacional de Salud de Chile 2016-2017.

BACKGROUND: Physical inactivity and sedentariness are independent risk factors for mortality. Physical inactivity is defined as engaging in insufficient moderate/vigorous physical activity (i.e. not meeting the WHO's recommendations). Sedentariness is defined according to sedentary behavior; evidence suggests that > 8 h/d could serve to consider a person as sedentary. The Chilean National Health Survey 2016-2017 (NHS), using a single question (Question-NHS), considered as "sedentary" those who did not engage in sports or physical activity for ≥ 30 min, ≥ 3 times/wk. Thus, it attempted to estimate sedentariness without considering sedentary behavior. AIM: To determine the prevalence of physical inactivity and sedentariness in Chile, and to contrast such results with the Question-NHS. MATERIAL AND METHODS: We analyzed data from 5564 participants of the 2016-2017 NHS, aged ≥ 18 years. The Global Physical Activity Questionnaire was used to determine moderate/vigorous physical activity and sedentary behavior. We defined physical inactivity as having < 600 MET × min/wk of moderate/vigorous physical activity, and sedentariness as having > 8 h/d of sedentary behavior. RESULTS: The prevalences [95% confidence intervals] of physical inactivity and sedentariness were 32% [29-34] and 6% [5-7] respectively, while 3% [2-4] were both physically inactive and sedentary. The Question-NHS classified 88% [86-89] as "sedentary", but among them, 35% were physically inactive and 6% were sedentary. CONCLUSIONS: One third of adults are inactive, one out of ten is sedentary, and one out of twenty is inactive and sedentary. The Question-NHS overestimates the population at risk.

Relative lipid oxidation associates directly with mitochondrial fusion phenotype and mitochondria-sarcoplasmic reticulum interactions in human skeletal muscle.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Twelve healthy men were included [mean (standard deviation), 24.7 (1.5) yr old, 24.4 (2.6) kg/m2]. The respiratory quotient (RQ) was used to estimate relative lipid oxidation at rest and during exercise (50% maximal oxygen consumption, 600 kcal expended). A skeletal muscle biopsy was obtained from the vastus lateralis at rest. Transmission electron microscopy was used to determine mitochondrial size and mitochondria-sarcoplasmic reticulum interactions (≤50 nm of distance between organelles). Protein levels of fusion/fission regulators were measured in skeletal muscle by Western blot. Resting RQ and exercise RQ associated inversely with intermyofibrillar mitochondrial size (r = -0.66 and r = -0.60, respectively, P < 0.05). Resting RQ also associated inversely with the percentage of intermyofibrillar mitochondria-sarcoplasmic reticulum interactions (r = -0.62, P = 0.03). Finally, intermyofibrillar mitochondrial size associated inversely with lipid droplet density (r = -0.66, P = 0.01) but directly with mitochondria fusion-to-fission ratio (r = 0.61, P = 0.03). Our results show that whole body lipid oxidation is associated with skeletal muscle intermyofibrillar mitochondrial size, fusion phenotype, and mitochondria-sarcoplasmic-reticulum interactions in nondiabetic humans.

Axillary web syndrome among Chilean women with breast cancer: incidence and possible predisposing factors.

PURPOSE: Breast cancer (BC) is the most common cancer in women worldwide. The main treatment for BC is surgery, which involves an axillary procedure that associates with the development of axillary web syndrome (AWS). The incidence of AWS among Chilean women with BC and its possible predisposing factors are currently unknown. Thus, we aimed to (1) determine the incidence of AWS among Chilean women with BC after surgery and (2) identify possible predisposing factors. METHODS: Within 90 days post-surgery, patients were assessed for AWS, i.e., palpable or visible axillary cords in the axillary region extending down from the mid-axilla to the ipsilateral arm. We then computed the odds ratio with 95% confidence interval (OR [95% CI]) for having AWS considering the following predisposing factors: age, body mass index (BMI), number of lymph nodes removed, axillary procedure, days from surgery to the physical therapy assessment, hospital for the surgery, type of breast surgery, and neoadyuvant chemotherapy. RESULTS: AWS was present in 49 out of 107 patients (45.8%). Younger age and lower BMI appeared as the sole predisposing factors for AWS (age, 0.95 [0.91-0.99]; BMI, normal weight 1.00, overweight 0.35 [0.11-1.12], obesity 0.28 [0.08-0.97]). CONCLUSION: The incidence of AWS among Chilean women with BC was 45.8%. Our study also confirms data from previous reports showing that younger age and low BMI are associated with the development of AWS.

Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle.

We hypothesized that a single session of resistance exercise performed in moderate hypoxic (FiO2: 14%) environmental conditions would potentiate the anabolic response during the recovery period spent in normoxia. Twenty subjects performed a 1-leg knee extension session in normoxic or hypoxic conditions. Muscle biopsies were taken 15 min and 4 h after exercise in the vastus lateralis of the exercised and the nonexercised legs. Blood and saliva samples were taken at regular intervals before, during, and after the exercise session. The muscle fractional-protein synthetic rate was determined by deuterium incorporation into proteins, and the protein-degradation rate was determined by methylhistidine release from skeletal muscle. We found that: 1) hypoxia blunted the activation of protein synthesis after resistance exercise; 2) hypoxia down-regulated the transcriptional program of autophagy; 3) hypoxia regulated the expression of genes involved in glucose metabolism at rest and the genes involved in myoblast differentiation and fusion and in muscle contraction machinery after exercise; and 4) the hypoxia-inducible factor-1α pathway was not activated at the time points studied. Contrary to our hypothesis, environmental hypoxia did not potentiate the short-term anabolic response after resistance exercise, but it initiated transcriptional regulations that could potentially translate into satellite cell incorporation and higher force production in the long term.-Gnimassou, O., Fernández-Verdejo, R., Brook, M., Naslain, D., Balan, E., Sayda, M., Cegielski, J., Nielens, H., Decottignies, A., Demoulin, J.-B., Smith, K., Atherton, P. J., Fancaux, M., Deldicque, L. Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle.

Physical activity levels and preferences of patients with breast cancer receiving chemotherapy in Chile.

PURPOSE: In Chilean patients with breast cancer (BC) receiving chemotherapy we aimed to (a) report the levels of physical activity (PA), (b) compare clinical/socio-demographic parameters among patients with different levels of PA, and (c) explore exercise preferences. METHODS: Patients (n = 112) completed a questionnaire regarding their PA habits, and another questionnaire regarding their preferences for an exercise program. Patients were then divided into three groups based on the exercise guidelines for patients with BC (150 min/week of moderate exercise, or 75 min/week of vigorous exercise). The groups were (i) not engaging in any moderate-to-vigorous PA (MVPA), (ii) engaging in some MVPA, but not meeting the guidelines, and (iii) meeting the guidelines. Clinical/socio-demographic parameters and preferences for exercise were compared between groups. RESULTS: Only 13% of patients with BC met the exercise guidelines. These patients were younger, had been diagnosed more recently, and had fewer children than patients not engaging in MVPA. There were no differences in the preferences for exercise between groups. Overall, patients preferred to exercise with other patients (76%), at moderate intensity (67%), performing different activities (94%), supervised (94%), with a fixed schedule (69%), and to do group activities (90%). CONCLUSION: Most patients with BC receiving chemotherapy did not meet the exercise guidelines. Patients > 50 years old and with > 2 children were the most inactive. Efforts to increase PA levels should focus especially on these patients. The preferences for exercise reported here will help to increase adherence to exercise programs and improve outcomes for these patients in Chile.

Basal Serum Cortisol and Testosterone/Cortisol Ratio Are Related to Rate of Na+ Lost During Exercise in Elite Soccer Players.

During exercise, the human body maintains optimal body temperature through thermoregulatory sweating, which implies the loss of water, sodium (Na+), and other electrolytes. Sweat rate and sweat Na+ concentration show high interindividual variability, even in individuals exercising under similar conditions. Testosterone and cortisol may regulate sweat Na+ loss by modifying the expression/activity of the cystic fibrosis transmembrane conductance regulator. This has not been tested. As a first approximation, the authors aimed to determine whether basal serum concentrations of testosterone or cortisol, or the testosterone/cortisol ratio relate to sweat Na+ loss during exercise. A total of 22 male elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise (basal). Sweat samples were collected during a training session, and sweat Na+ concentration was determined. The basal serum concentrations of testosterone and cortisol and their ratio were (mean [SD]) 13.6 (3.3) pg/ml, 228.9 (41.4) ng/ml, and 0.06 (0.02), respectively. During exercise, the rate of Na+ loss was related to cortisol (r = .43; p < .05) and to the testosterone/cortisol ratio (r = -.46; p < .01), independently of the sweating rate. The results suggest that cortisol and the testosterone/cortisol ratio may influence Na+ loss during exercise. It is unknown whether this regulation depends on the cystic fibrosis transmembrane conductance regulator.

Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity.

Metabolic flexibility to lipid (MetFlex-lip) is the capacity to adapt lipid oxidation to lipid availability. Hypothetically, impaired MetFlex-lip in skeletal muscle induces accumulation of lipid metabolites that interfere with insulin signaling. Our aim was to compare MetFlex-lip during exercise in subjects with low (Low_IS) vs. high (High_IS) insulin sensitivity. Twenty healthy men were designated as Low_IS or High_IS on the basis of the median of the homeostatic model assessment of insulin resistance index. Groups had similar age, body mass index, and maximum oxygen uptake (V̇o2max). Subjects cycled at 50% V̇o2max until expending 650 kcal. Adaptation in lipid oxidation was calculated as the drop in respiratory quotient (RQ) at the end of exercise vs. the maximum RQ (ΔRQ). Lipid availability was calculated as the increase in circulating nonesterified fatty acids (NEFA) at the end of exercise vs. the minimum NEFA (ΔNEFA). ΔRQ as a function of ΔNEFA was used to determine MetFlex-lip. On average, RQ and circulating NEFA changed similarly in both groups. However, ΔRQ correlated with ΔNEFA in High_IS ( r = -0.83, P < 0.01) but not in Low_IS ( r = -0.25, P = 0.48) subjects. Thus the slope of the ΔRQ vs. ΔNEFA relationship was steeper in High_IS vs. Low_IS subjects (-0.139 ± 0.03 vs. -0.025 ± 0.03 RQ·mmol-1·l-1, respectively; P < 0.05), with similar intercepts. We conclude that in subjects with High_IS lipid-to-carbohydrate oxidation ratio adapts to the increased circulating NEFA availability during exercise. Such MetFlex-lip appears impaired in subjects with Low_IS. Whether a cause-effect relationship exists between impaired MetFlex-lip and low insulin sensitivity remains to be determined.

Validity of predictive equations for resting metabolic rate in healthy humans.

Background: There are several predictive equations for estimating resting metabolic rate (RMR) in healthy humans. Concordance of these equations against measured RMR is variable, and often dependent on the extent of RMR. Part of the discrepancy may be due to an insufficient accuracy of metabolic carts, but this accuracy can be improved via a correction procedure. Objective: To determine the validity of predictive RMR equations by comparing them against measured and corrected (i.e. the reference) RMR. Methods: RMR was measured, in 69 healthy volunteers (29 males/40 females; 32±8 years old; BMI 25.5±3.8 kg/m2) and then corrected by simulating gas exchange through pure gases and high-precision mass-flow regulators. RMR was predicted using 13 published equations. Bland-Altman analyses compared predicted vs. reference RMRs. Results: All equations correlated well with the reference RMR (r>0.67; P<0.0001), but on average, over-predicted the reference RMR (89-312 kcal/d; P<0.05). Based on Bland-Altman analyses, 12 equations showed a constant bias across RMR, but the bias was not different from zero for nine of them. Three equations stood out because the absolute difference between predicted and reference RMR was equal or lower than 200 kcal/d for >60% of individuals (the Mifflin, Oxford and Müller equations). From them, only the Oxford equations performed better in both males and females separately. Conclusion: The Oxford equations are a valid alternative to predict RMR in healthy adult humans. Gas-exchange correction appears to be a good practice for the reliable assessment of RMR.

Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training.

Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Skeletal muscles of ATF3-knockout (ATF3-KO) and control mice were analyzed at rest, after exercise, and after training. In resting muscles, there was no difference between genotypes in enzymatic activities or fiber type. After exercise, a microarray analysis in quadriceps revealed ATF3 affects genes modulating chemotaxis and chemokine/cytokine activity. Quantitative PCR showed that the mRNA levels of chemokine C-C motif ligand (ccl)8 and chemokine C-X-C motif ligand (cxcl)13 were higher in quadriceps of ATF3-KO mice than in control mice. The same was observed for ccl9 and cxcl13 in soleus. Also in soleus, ccl2, interleukin (il)6, il1ß, and cluster of differentiation (cd)68 mRNA levels increased after exercise only in ATF3-KO mice. Endurance training increased the basal mRNA level of hexokinase-2, hormone sensitive lipase, glutathione peroxidase-1, and myosin heavy chain IIa in quadriceps of control mice but not in ATF3-KO mice. In summary, ATF3 attenuates the expression of inflammation-related genes after exercise and thus facilitates molecular adaptation to training.-Fernández-Verdejo, R., Vanwynsberghe, A. M., Essaghir, A., Demoulin, J.-B., Hai, T., Deldicque, L., Francaux, M. Activating transcription factor 3 attenuates chemokine and cytokine expression in mouse skeletal muscle after exercise and facilitates molecular adaptation to endurance training.

IRE1α and TRB3 do not contribute to the disruption of proximal insulin signaling caused by palmitate in C2C12 myotubes.

Endoplasmic reticulum (ER) stress is a central actor in the physiopathology of insulin resistance (IR) in various tissues. The subsequent unfolded protein response (UPR) interacts with insulin signaling through inositol-requiring 1α (IRE1α) activation and tribbles homolog 3 (TRB3) expressions. IRE1α impairs insulin actions through the activation of c-Jun N-terminal kinase (JNK), and TRB3 is a pseudokinase inhibiting Akt. In muscle cells, the link between ER stress and IR has only been demonstrated by using chemical ER stress inducers or overexpression techniques. However, the involvement of ER stress in lipid-induced muscle IR remains controversial. The aim of the study is to test whether palmitate-induced IRE1α signaling and TRB3 expression disturb insulin signaling in myogenic cells. C2C12 myotubes were exposed to palmitate and then stimulated with insulin. siRNA transfection was used to downregulate TRB3 and IRE1α. Palmitate increased TRB3 expression, activated IRE1α signaling, and reduced the insulin-dependent Akt phosphorylation. Knocking down TRB3 or IRE1α did not prevent the inhibitory effect of palmitate on Akt phosphorylation. Our results support the idea that ER stress is not responsible for lipid-induced IR in C2C12 myotubes.

Electrical stimulation induces IL-6 in skeletal muscle through extracellular ATP by activating Ca(2+) signals and an IL-6 autocrine loop.

Interleukin-6 (IL-6) is an important myokine that is highly expressed in skeletal muscle cells upon exercise. We assessed IL-6 expression in response to electrical stimulation (ES) or extracellular ATP as a known mediator of the excitation-transcription mechanism in skeletal muscle. We examined whether the canonical signaling cascade downstream of IL-6 (IL-6/JAK2/STAT3) also responds to muscle cell excitation, concluding that IL-6 influences its own expression through a positive loop. Either ES or exogenous ATP (100 µM) increased both IL-6 expression and p-STAT3 levels in rat myotubes, a process inhibited by 100 µM suramin and 2 U/ml apyrase. ATP also evoked IL-6 expression in both isolated skeletal fibers and extracts derived from whole FDB muscles. ATP increased IL-6 release up to 10-fold. STAT3 activation evoked by ATP was abolished by the JAK2 inhibitor HBC. Blockade of secreted IL-6 with a neutralizing antibody or preincubation with the STAT3 inhibitor VIII reduced STAT3 activation evoked by extracellular ATP by 70%. Inhibitor VIII also reduced by 70% IL-6 expression evoked by ATP, suggesting a positive IL-6 loop. In addition, ATP increased up to 60% the protein levels of SOCS3, a negative regulator of the IL-6 signaling pathway. On the other hand, intracellular calcium chelation or blockade of IP3-dependent calcium signals abolished STAT3 phosphorylation evoked by either extracellular ATP or ES. These results suggest that expression of IL-6 in stimulated skeletal muscle cells is mediated by extracellular ATP and nucleotide receptors, involving IP3-dependent calcium signals as an early step that triggers a positive IL-6 autocrine loop.

Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling.

Excessive accumulation of intermuscular adipose tissue (IMAT) is a common pathological feature in various metabolic and health conditions and can cause muscle atrophy, reduced function, inflammation, insulin resistance, cardiovascular issues, and unhealthy aging. Although IMAT results from fat accumulation in muscle, the mechanisms underlying its onset, development, cellular components, and functions remain unclear. IMAT levels are influenced by several factors, such as changes in the tissue environment, muscle type and origin, extent and duration of trauma, and persistent activation of fibro-adipogenic progenitors (FAPs). FAPs are a diverse and transcriptionally heterogeneous population of stromal cells essential for tissue maintenance, neuromuscular stability, and tissue regeneration. However, in cases of chronic inflammation and pathological conditions, FAPs expand and differentiate into adipocytes, resulting in the development of abnormal and ectopic IMAT. This review discusses the role of FAPs in adipogenesis and how they remodel IMAT. It highlights evidence supporting FAPs and FAP-derived adipocytes as constituents of IMAT, emphasizing their significance in adipose tissue maintenance and development, as well as their involvement in metabolic disorders, chronic pathologies and diseases. We also investigated the intricate molecular pathways and cell interactions governing FAP behavior, adipogenesis, and IMAT accumulation in chronic diseases and muscle deconditioning. Finally, we hypothesize that impaired cellular metabolic flexibility in dysfunctional muscles impacts FAPs, leading to IMAT. A deeper understanding of the biology of IMAT accumulation and the mechanisms regulating FAP behavior and fate are essential for the development of new therapeutic strategies for several debilitating conditions.

Mitochondria-SR interaction and mitochondrial fusion/fission in the regulation of skeletal muscle metabolism.

Mitochondria-endoplasmic/sarcoplasmic reticulum (ER/SR) interaction and mitochondrial fusion/fission are critical processes that influence substrate oxidation. This narrative review summarizes the evidence on the effects of substrate availability on mitochondrial-SR interaction and mitochondria fusion/fission dynamics to modulate substrate oxidation in human skeletal muscle. Evidence shows that an increase in mitochondria-SR interaction and mitochondrial fusion are associated with elevated fatty acid oxidation. In contrast, a decrease in mitochondria-SR interaction and an increase in mitochondrial fission are associated with an elevated glycolytic activity. Based on the evidence reviewed, we postulate two hypotheses for the link between mitochondrial dynamics and insulin resistance in human skeletal muscle. First, glucose and fatty acid availability modifies mitochondria-SR interaction and mitochondrial fusion/fission to help the cell to adapt substrate oxidation appropriately. Individuals with an impaired response to these substrate challenges will accumulate lipid species and develop insulin resistance in skeletal muscle. Second, a chronically elevated substrate availability (e.g. overfeeding) increases mitochondrial production of reactive oxygen species and induced mitochondrial fission. This decreases fatty acid oxidation, thus leading to the accumulation of lipid species and insulin resistance in skeletal muscle. Altogether, we propose mitochondrial dynamics as a potential target for disturbances associated with low fatty acid oxidation.

Tailored Informational Interventions for Reducing Surplus and Waste of Fruits and Vegetables in a Food Market: A Pilot Study.

This pilot study explored the effectiveness of tailored informational interventions to reduce the surplus and waste of fruits and vegetables at the distribution level in Chile. Stalls from a fresh food market were randomized to intervention (n = 5 selling fruits, n = 5 selling vegetables) or control (n = 4 selling fruits, n = 4 selling vegetables) groups. The causes of surplus and waste were estimated by questionnaires. Surplus, avoidable waste, and unavoidable waste were measured using direct quantification before and after the intervention, and were expressed relative to the initial stock. Before the intervention, the surplus was (median [25th-75th percentile]) 46.2% [33.3-51.2] for fruits and 51.5% [41.3-55.0] for vegetables; avoidable waste was 0.1% [0.0-0.8] for fruits and 1.8% [0.7-5.3] for vegetables; and unavoidable waste was 0.0% [0.0-1.0] for fruits and 0.0% [0.0-1.3] for vegetables. Planning and storage represented the main causes explaining surplus and waste. After the intervention, the intervention group decreased the surplus of fruits compared to the control group (-17.8% [-29.0--11.0] vs. 5.8% [-0.6-7.8], respectively; p = 0.016), without other differences. In conclusion, tailored informational interventions based on the causes of surplus and waste may reduce the surplus of fruits in a fresh food market. Interventions might also include management strategies for the surplus to improve grocers' business operations.