Fat Storage Research Articles

From fat storage to immune hubs: the emerging role of adipocytes in coordinating the immune response to infection.

Adipose tissue is a rich source of diverse cell populations, including immune cells, adipocytes and stromal cells. Interactions between these different cell types are now appreciated to be critical for maintaining tissue structure and function, by governing processes such as adipogenesis, lipolysis and differentiation of white to beige adipocytes. Interactions between these cells also drive inflammation in obesity, leading to an expansion of adipose tissue immune cells, and the secretion of proinflammatory cytokines from immune cells and from adipocytes themselves. However, in evolutionary terms, obesity is a recent phenomenon, raising the question of why adipocytes evolved to express factors that influence the immune response. Studies of various pathogens indicate that adipocytes are highly responsive to infection, altering their metabolic profiles in a way that can be used to release nutrients and fuel the immune response. In the case of infection with the extracellular parasite Trypanosoma brucei, attenuating the ability of adipocytes to sense the cytokine IL-17 results in a loss of control of the local immune response and an increased pathogen load. Intriguingly, comparisons of the adipocyte response to infection suggest that the immune responses of these cells occur in a pathogen-dependent manner, further confirming their complexity. Here, with a focus on murine adipose tissue, we discuss the emerging concept that, in addition to their canonical function, adipocytes are immune signalling hubs that integrate and disseminate signals from the immune system to generate a local environment conducive to pathogen clearance.

Visceral adipose tissue, epicardial fat, and hepatic steatosis in polycystic ovary syndrome: a study of ectopic fat stores and metabolic dysfunction.

In polycystic ovary syndrome (PCOS), ectopic fat accumulation remains debatable. Therefore, intra-abdominal, hepatic, and epicardial fat were compared between PCOS women and body mass index (BMI)-matched controls and their associations with metabolic and hormonal parameters were explored. Furthermore, the performance of echocardiographic epicardial adipose tissue thickness (EATT) and hepatic steatosis measurement using transient elastography-based controlled attenuation parameter (TE-CAP) in screening abdominal visceral adipose tissue (VAT) was originally evaluated. Women aged 18-39 years with BMI < 35 kg/m² were recruited. PCOS was defined by the Rotterdam criteria. All participants underwent clinical and laboratory exams, dual-energy X-ray absorptiometry (DXA), TE-CAP, and echocardiography. A receiver operating characteristic curve was applied to evaluate the accuracy and optimal cutoff values of TE-CAP and EATT in predicting DXA-measured VAT. The study included 35 women with PCOS and 37 controls. PCOS women exhibited higher levels of androgens, insulin resistance (IR) parameters, LDL-cholesterol, triglycerides, VAT, and EATT. VAT correlated with IR and triglycerides, whereas EATT correlated with HDL-cholesterol. In PCOS women aged 18-29, the cutoff values of CAP and EATT for VAT were 198.0 and 3.07, respectively, with CAP showing higher area under the curves (AUC). In PCOS women aged 30-39, the cutoff values were 209.5 and 3.36, respectively, with EATT showing higher AUC. VAT correlates with more metabolic parameters in PCOS than TE-CAP or EATT. TE-CAP is useful for VAT screening in PCOS patients aged 18-39 years, whereas EATT is effective and outperforms CAP in those aged 30-39 years.

Physiological and behavioral variation by urbanization and climate in an urban-tolerant toad

The distribution of a species is best understood by examining the organism-environment interaction. Climate and anthropogenic habitat degradation, including urbanization, are salient features of the environment that can limit species distributions, especially for ectotherms. Comparative studies of the capacity of individuals to cope with rapid environmental change can help us understand the future success or failure of local populations or even the species. Studies of the glucocorticoid stress response are commonly used to understand how species cope with environmental stressors. Glucocorticoids modulate many aspects of physiological homeostasis including changes in energetic allocation and behavior. In a time of global amphibian decline the Gulf Coast Toad (Incilius nebulifer) is increasing its distribution and abundance. To understand how this species deals with thermal and urban stressors, we studied glucocorticoid regulation, hop performance, and lipid storage in I. nebulifer juveniles across nine populations that differed in average annual temperature and level of imperviousness (as an indication of urbanization). We measured corticosterone release rates at baseline, during agitation stress, and during recovery; then measured locomotor performance and whole-body lipids. We tested if I. nebulifer in hotter temperatures and more urbanized habitats exhibits elevated baseline corticosterone levels and either a reduced corticosterone stress response (“stress resistance” hypothesis) or quick post-stress recovery by negative feedback (“on again, off again” hypothesis). We also tested whether they exhibit reduced fat stores and decreased locomotor performance as costs of dealing with thermal and urban stressors. We found that I. nebulifer showed elevated baseline and agitation (stressed-induced) corticosterone release rates, and higher lipid storage with increasing urbanization. Climate had quadratic effects on these traits, such that populations living at the lowest and highest temperatures had the lowest corticosterone release rates and lipid stores, and the highest hop performance was observed in the least urbanized site at the warmest climate. Additionally, the rate of glucocorticoid recovery after agitation (negative feedback) decreased with increasing temperature and increased with increasing urbanization. These results indicate that I. nebulifer follows the “on again, off again” hypothesis in an adaptive pattern, which may help them cope with environmental change in terms of urbanization and climatic differences.

High-fat and high-sugar diets induce rapid adaptations of fat storage in the house fly Musca domestica L.

Dietary change can be a strong evolutionary force and lead to rapid adaptation in organisms. High-fat and high-sugar diets can challenge key metabolic pathways, negatively affecting other life-history traits and inducing pathologies such as obesity and diabetes. In this study we use experimental evolution to investigate the plastic and evolutionary responses to nutritionally unbalanced diets. We reared replicated lines of larvae of the housefly Musca domestica on a fat-enriched (FAT), a sugar-enriched (SUG), and a control (CTRL) diet for thirteen generations. We measured development time in each generation, and larval growth and fat accumulation in generation 1, 7, and 13. Subsequently all lines were reared for one generation on the control diet to detect any plastic and evolutionary changes. In the first generation, time to pupation decreased on a fat-rich diet and increased on a sugar-rich diet. The fat-rich diet increased fat accumulation and, to a lesser extent, dry weight of the larvae. Multigenerational exposure to the unbalanced diets caused compensatory changes in development time, dry weight, as well as absolute and relative fat content, although pattern and timing depended on diet and trait. When put back on a control diet, many of the changes induced by the unbalanced diets disappeared, indicating that diet has large plastic effects. Nevertheless, fat-evolved lines still grew significantly larger than the sugar-evolved lines, and sugar-evolved lines had consistently lower fat content. This can be an effect of parental diet or an evolutionary change in nutrient metabolism as a consequence of multigenerational exposure to unbalanced diets.

Rising global temperatures and its impact on sleep behavior of male redheaded bunting (Emberiza bruniceps).

Anthropogenic global warming is one of the most pervasive threats to nature and biodiversity. The magnitude with which earths' temperature is rising is affecting every lifeform uniquely; however, the studies highlighting the impacts of global warming on avian sleep are scarce. To this end, the present study was aimed at analyzing the impact of global warming on sleep behavior of a nocturnal migrant, Emberiza bruniceps. For this purpose, the birds were divided into two groups (N = 15 each), subjected to high (35 ± 1°C) and low (19 ± 1°C) temperature schedule with concurrent exposure to 8L:16D (short day; SD) photoperiod followed by 13L:11D (long day; LD). The experiment continued till 7 cycles of zugunruhe (LD) in birds. The results reveal significant impact of temperature treatment on initiation and quality of zugunruhe. Temporal distribution of activity and rest varied according to the temperature provided. Focusing on rest and specifically on sleep of birds, high ambient temperatures resulted in greater sleep fragmentation (evident by increased awakenings during night), whereas low temperature created a sleep conducive environment (evident by abundance of back sleep). Besides postural differences, high temperature resulted in reduced sleep duration, sleep onset latency and circulating plasma melatonin levels in comparison with low temperature suggesting the negative impact of high temperature on different sleep attributes. Not only sleep, seasonal physiology of birds such as hyperphagia, gain in body mass, and fat stores showed significant reduction in high temperature condition. Besides behavioral and physiological alterations, high ambient temperature led to elevated expression of temperature sensitive (trpv4, trpm8, hspa8, and hsp70) genes. Enhanced expression of chrm3 (responsible for wakefulness) also affirms sleep fragmentation in response to high temperature. Thus, the study highlights the negative impact of high temperature on birds' sleep behavior and seasonal physiology.

Developmental histology of the liver in the Balkan crested newt Triturus ivanbureschi (Caudata: Salamandridae)

The liver, a crucial organ for metabolic processes, has a generally uniform histological structure across amphibian taxa. However, ontogenetic changes, particularly those related to biphasic life cycle and metamorphosis, are less documented. Here, we explored and described the liver histology of an emerging model organism, the Balkan crested newt (Triturus ivanbureschi) at three ontogenetic stages: larval, juvenile (just after metamorphosis) and adult. At the larval stage, the liver is characterized by hepatocytes containing large lipid droplets, poorly developed basement membranes in the blood vessels, and a lack of melanin-rich macrophage centers. Juveniles show transitional characteristics between larvae and adults. Lipid droplets in hepatocytes are abundant, but also, at the juvenile stage the well-developed basement membrane of blood vessels and melanomacrophages are present, as in adults. The presence of lipid droplets in hepatocytes during larval and juvenile stages suggests the liver's role in fat storage and energy provision during development and growth. Melanomacrophages, which synthesize melanin, perform phagocytosis, and neutralize free radicals, have been found in juveniles (after metamorphosis) and increase with age. The biphasic life cycle and liver histology transition in Triturus newts provide an insight in changes in liver histology and make them a suitable model for studying fat deposition regulation and the evolution of the immune system in terrestrial vertebrates.

Effect of the Composition of the Mediterranean Diet on Body Mass Index, Waist Circumference, Fat Level, and Visceral Fat in Patients with Obesity

Excessive and unhealthy fat storage is known as obesity. Both monounsaturated and polyunsaturated fatty acids are highly encouraged in the Mediterranean diet. Obese patients at a Bandung clinic were studied to examine how the Mediterranean diet affects their BMI, waist size, fat percentage, and visceral fat. Analytical observational methods utilizing prospective cohort observations were employed. A systematic random sample technique was used to carry out the sampling. Participants were 34 overweight individuals who had twelve monthly food pattern assessments and two monthly examinations for body mass index (BMI), waist size, fat percentage, and visceral fat. To compare proportions between the rMED adherence groups and to look for differences in the composition of the Mediterranean diet on BMI, waist circumference, fat content, and visceral fat, we used the ANOVA test and Tuckey’s post-hoc test. In addition, the eight tenets of the Mediterranean diet were assessed using linear regression. The average age of the obese patients who followed the Mediterranean diet was 57.54 years, and 79.41% of them were female. It was found that the components of vegetables, fruits, nuts, seafood, and dairy products had a substantial impact on the body mass index of the participants, while the components of vegetables, fruits, nuts, legumes, seeds, meat, fish, olive oil, and dairy products did not have a significant impact on the waist circumference, fat content, or visceral fat. Keywords: body mass index, fat content Mediterranean diet composition, obesity, visceral fat, waist circumference

GCKIII kinases control hepatocellular lipid homeostasis via shared mode of action

Metabolic dysfunction–associated steatotic liver disease has emerged as a leading global cause of chronic liver disease. Our recent translational investigations have shown that the STE20-type kinases comprising the GCKIII subfamily—MST3, STK25, and MST4—associate with hepatic lipid droplets and regulate ectopic fat storage in the liver; however, the mode of action of these proteins remains to be resolved. By comparing different combinations of the silencing of MST3, STK25, and/or MST4 in immortalized human hepatocytes, we found that their single knockdown results in a similar reduction in hepatocellular lipid content and metabolic stress, without any additive or synergistic effects observed when all three kinases are simultaneously depleted. A genome-wide yeast two-hybrid screen of the human hepatocyte library identified several interaction partners contributing to the GCKIII-mediated regulation of liver lipid homeostasis, that is, PDCD10 that protects MST3, STK25, and MST4 from degradation, MAP4K4 that regulates their activity via phosphorylation, and HSD17B11 that controls their action via a conformational change. Finally, using in vitro kinase assays on microfluidic microarrays, we pinpointed various downstream targets that are phosphorylated by the GCKIII kinases, with known functions in lipogenesis, lipolysis, and lipid secretion, as well as glucose uptake, glycolysis, hexosamine synthesis, and ubiquitination. Together, this study demonstrates that the members of the GCKIII kinase subfamily regulate hepatocyte lipid metabolism via common pathways. The results shed new light on the role of MST3, STK25, and MST4, as well as their interactions with PDCD10, MAP4K4, and HSD17B11, in the control of liver lipid homeostasis and metabolic dysfunction–associated steatotic liver disease susceptibility.

Glucagon-like peptide-1 receptor agonist-based agents and weight loss composition: Filling the gaps.

Excess adiposity is at the root of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as first-line treatments for T2D based on significant weight loss results. The composition of weight loss using most diets consists of <25% fat-free mass (FFM) loss, with the remainder from fat stores. Higher amounts of weight loss (achieved with metabolic bariatric surgery) result in greater reductions in FFM. Our aim was to assess the impact that GLP-1RA-based treatments have on FFM. We analysed studies that reported changes in FFM with the following agents: exenatide, liraglutide, semaglutide, and the dual incretin receptor agonist tirzepatide. We performed an analysis of various weight loss interventions to provide a reference for expected changes in FFM. We evaluated studies using dual-energy X-ray absorptiometry (DXA) for measuring FFM (a crude surrogate for skeletal muscle). In evaluating the composition of weight loss, the percentage lost as fat-free mass (%FFML) was equal to ΔFFM/total weight change. The %FFML using GLP-1RA-based agents was between 20% and 40%. In the 28 clinical trials evaluated, the proportion of FFM loss was highly variable, but the majority reported %FFML exceeding 25%. Our review was limited to small substudies and the use of DXA, which does not measure skeletal muscle mass directly. Since FFM contains a variable amount of muscle (approximately 55%), this indirect measure may explain the heterogeneity in the data. Assessing quantity and quality of skeletal muscle using advanced imaging (magnetic resonance imaging) with functional testing will help fill the gaps in our current understanding.

Brain gene expression reveals pathways underlying nocturnal migratory restlessness

Migration is one of the most extreme and energy demanding life history strategies to have evolved in the animal kingdom. In birds, champions of long-distance migrations, the seasonal emergence of the migratory phenotype is characterised by rapid physiological and metabolic remodelling, including substantial accumulation of fat stores and increases in nocturnality. The molecular underpinnings and brain adaptations to seasonal migrations remain poorly understood. Here, we exposed Common quails (Coturnix coturnix) to controlled changes in day length to simulate southward autumn migration, and then blocked the photoperiod until birds entered the non-migratory wintering phase. We first performed de novo RNA-Sequencing from selected brain samples (hypothalamus) collected from birds at a standardised time at night, either in a migratory state (when restlessness was highest and at their body mass peak), or in a non-migratory state and conducted differential gene expression and functional pathways analyses. We found that the migratory state was associated with up-regulation of a few, yet functionally well defined, gene expression networks implicated in fat trafficking, protein and carbohydrate metabolism. Further analyses that focused on candidate genes (apolipoprotein H or APOH, lysosomal associated membrane protein-2 or LAMP2) from samples collected during the day or night across the entire study population suggested differences in the expression of these genes depending on the time of the day with the largest expression levels being found in the migratory birds sampled at night. We also found that expression of APOH was positively associated with levels of nocturnal activity in the migratory birds; such an association was absent within the non-migratory birds. Our results provide novel experimental evidence revealing that hypothalamic changes in expression of apolipoprotein pathways, which regulate the circulatory transport of lipids, are likely key regulatory activators of nocturnal migratory movements. Our study paves the way for performing deeper functional investigations on seasonal molecular remodelling underlying the development of the migratory phenotype.

Do diet and Fumagillin treatment impact Vairimorpha (Nosema) spp. (Microspora: Nosematidae) infections in honey bees (Hymenoptera: Apidae) and improve survival and growth of colonies overwintered in cold storage?

Vairimorpha (Microsporidia: Nosematidae)is a microsporidian that infects honey bees especially in winter. Fumagillin can reduce infections, but whether overwintering survival is improved is unclear. The diet also may influence the severity of Nosema infections. We examined the relationship between Nosema and colony size and survival in hives overwintered in cold storage facilities. In year 1, no Fumagillin treatments were applied. Colony size and survival after cold storage and almond bloom were comparable between groups with high and low pre-cold storage infections. In year 2, size and survival were compared among colonies with and without Fumagillin treatment that were fed either pollen or protein supplement prior to overwintering. Colonies treated with Fumagillin had lower spore numbers than untreated, but colony sizes and survival were similar among the treatments. However, more colonies with zero spores per bee could be rented for almond pollination and were alive after bloom than those averaging >1 million spores per bee. Fat body metrics can affect overwintering success. In both years, fat body weights and protein concentrations increased, and lipid concentrations decreased while bees were in cold storage. Fat body metrics did not differ with Nosema infection levels. However, Fumagillin negatively affected pre-cold storage fat body protein concentrations and colony sizes after cold storage and almond bloom. Treating with Fumagillin before overwintering in cold storage might result in greater colony survival if spore numbers are high, but undetectable or even negative effects when spore numbers are low.

A fluorescence lifetime-based novel method for accurate lipid quantification of BODIPY vital-stained C. elegans

Lipid droplets (LDs) are organelles associated with lipid storage and energy metabolism; thus, their morphology and quantity are of significant research interest. While commercially available BODIPY dye effectively labels LDs in various cell types, it also labels lysosome-related organelles (LROs) in C. elegans, leading to non-specific LD quantification. Here, we report that the fluorescent signals of BODIPY exhibit distinct fluorescence lifetime patterns for LROs and LDs, which can be captured, visualized, and filtered by fluorescence lifetime imaging microscopy. Furthermore, we proposed and validated a method based on fluorescence lifetime that can improve the accuracy of fat storage quantification in BODIPY vital-staining worms, which holds broad applications, including rapid and accurate LD quantification in forward genetic screening. Additionally, our method enables observing dynamic LD-LRO interactions in living worms, a unique capability of BODIPY vital staining. Our findings highlight distinct BODIPY fluorescence lifetime characteristics of LDs and LROs, providing a valuable tool for future research on LDs, LROs, or their interactions.

Fat storage and drought tolerance in a seasonally‐adapted primate: Implications for modeling the effects of animal responses to global climate change

AbstractGlobal warming is changing habitats and affecting biodiversity, and is expected to exacerbate aridification in many regions. Animals and plants in seasonally dry tropical forests often exhibit adaptations to cope with seasonal resource limitation. However, whether these adaptations will facilitate drought tolerance or increase drought vulnerability is unclear. Here, we combine long‐term individual‐based data on phenology, morphometrics, and demographics to investigate how drought impacts the food resources, health, reproduction, and behavior of a population of Verreaux's sifaka (Propithecus verreauxi), a critically endangered lemur inhabiting dry deciduous forests in Madagascar. Between December 2010 and May 2023, the population experienced 3 years of severe drought (2016, 2017, 2022). During green periods in severe drought, the availability of high‐quality sifaka foods (young leaves, fruit) was significantly reduced and fruit tree mortality increased. This reduced availability of fruit persisted in the year after a drought, despite typical rainfall. Yet surprisingly, we found no negative effects on body condition or commonly‐used metrics for reproductive success during drought years or years following a drought. Instead, sifaka exhibited significantly higher levels of subcutaneous body fat during severe droughts. We observed little change in sifaka behavior between drought and non‐drought periods. However, they were more likely to lick dew during severe drought, and spent significantly less time feeding on young and mature leaves. They also significantly increased their time feeding on flowers and fruits, despite the reduced abundance of fruit in the habitat. Together, our results suggest that increased consumption of water‐rich fruit and flowers during severe droughts could facilitate physiological mechanisms that help sifaka cope with water scarcity, including fructose‐mediated fat storage, metabolic water production, and water conservation. These results provide new insights into how critically endangered animals may respond to climate change, suggesting that behavioral and physiological adaptations to seasonal resource limitation may buffer some mammals from the effects of severe drought or other extreme weather events.

What do frog calls tell us about males? The advertisement call of Physalaemus albifrons (Amphibia: Leptodactylidae) in the Brazilian semiarid region does not reflect either gonadal investment or energy storage

ABSTRACT Anuran advertisement calls can provide accurate information on the reproductive quality of the male callers, thus providing females with indicators for the selection of mates. Body size is generally correlated with the dominant frequency of male advertisement calls. However, it is unclear whether and to what extent call parameters are associated with gonadal investment and the energy reserves of the males. Given that in tropical seasonally dry environments the wet season is very short, gathering information about gonadal investment and energy reserves of mates should be particularly important. In the present study, we evaluated the relationship between acoustic performance, gonadal condition, and fat storage in the Neotropical frog Physalaemus albifrons from the Brazilian semiarid region, testing the hypothesis that the advertisement call (repetition rate, call duration, and fundamental and dominant frequencies) would be a good predictor of male quality in terms of gonadal investment (testicle length) and energy reserves (mass of fat bodies). Contrary to our predictions, neither testicle length nor the mass of fat bodies was related to any of the acoustic parameters of the advertisement calls of P. albifrons. These results indicate that the advertisement call of P. albifrons does not provide reliable information on gonadal investment or energy storage of males. Possibly, in habitats with little and unpredictable rainfall, males of P. albifrons should present small variation in gonadal and fat storage conditions during its short reproductive window. Our findings contribute to the understanding of anuran reproductive strategies in seasonally dry environments.

Impact of Sex on the Therapeutic Efficacy of Rosiglitazone in Modulating White Adipose Tissue Function and Insulin Sensitivity.

Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic target. Rosiglitazone (RSG), a potent PPARγ agonist, promotes healthy WAT growth and mitochondrial function through MitoNEET modulation. Recent RSG-based strategies specifically target white adipocytes, avoiding side effects. Our aim was to investigate whether sex-specific differences in the insulin-sensitizing effects of RSG exist on WAT during obesity and inflammation. We used Wistar rats of both sexes fed a high-fat diet (HFD, 22.5% fat content) for 16 weeks. Two weeks before sacrifice, a group of HFD-fed rats received RSG treatment (4 mg/kg of body weight per day) within the diet. HFD male rats showed greater insulin resistance, inflammation, mitochondrial dysfunction, and dyslipidemia than females. RSG had more pronounced effects in males, significantly improving insulin sensitivity, fat storage, mitochondrial function, and lipid handling in WAT while reducing ectopic fat deposition and enhancing adiponectin signaling in the liver. Our study suggests a significant sexual dimorphism in the anti-diabetic effects of RSG on WAT, correlating with the severity of metabolic dysfunction.

An acute handling challenge mobilizes glucose and free fatty acids in mountain Dark-eyed Juncos (Junco hyemalis oreganus)

Resource mobilization and reallocation is a major endpoint of the physiological response to acute challenges. However, energy metabolites have not been the focus of most field studies. Here, we characterized the glycemic and free fatty acid (FFA) response to an acute-handling challenge in a breeding, free-living, population of Mountain Dark-eyed Juncos ( Junco hyemalis oreganus) in Mono County, CA. Juncos ( n = 12) were trapped in seed-baited potter traps at Tioga Pass Meadow, coinciding with territory establishment and early nesting period. Blood samples were collected at 0, 15, and 30 min post-capture, and analysis showed Juncos mobilized both glucose and FFA in response to an acute handling challenge. Blood glucose levels were significantly higher than baseline at 15 min (42.6% increase) and 30 min post-capture (66.7% increase). FFA levels were also significantly higher than baseline at 15 min (29.2% increase) and 30 min post-capture (22% increase). We also measured morphometrics (e.g., wing chord length, tarsus length, etc.), fat, and mass for each individual to investigate the effects of body size and fat storage on energy mobilization using linear models. We found no significant effects of body size or fat and mass on FFA mobilization. However, body size had a significant effect on glucose mobilization, with larger individuals displaying a higher percent increase in glucose from baseline to 15 min. Additionally, we found an effect of sex on glucose mobilization, with males showing a higher percent increase in glucose from baseline to 15 min. These results suggest that energy mobilization capacity is influenced by body size and male Juncos may increase energy mobilization relative to females during the breeding season.

Murine nuclear tyrosyl-tRNA synthetase deficiency leads to fat storage deficiency and hearing loss

Aminoacyl-tRNA synthetases are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (YarsΔNLS) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, YarsΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, YarsΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aminoacyl-tRNA synthetases' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency.

Visceral Fat Increases Cardiometabolic Risk Factors Among Type 2 Diabetes Patients

The aim of this study is to discuss the increase in risk for obesity-related disorders. It is believed that such complications arise due to store of visceral fat. The visceral fat is considered as an independent predictor of all-cause of mortality among type 2 diabetes (T2D) patients. Higher visceral fat is associated with an adverse lipid and glucose profile. Accumulation of visceral fat is located inside the abdominal cavity and surrounds internal organs, such as in the liver, stomach, kidneys, pancreas, intestines, and heart. Store of visceral adipose tissue (VAT) is characterized as pro-inflammatory, metabolically active, and susceptible to lipolysis. This study tries to present briefly the harmful activities of visceral fat in human body.

Influence of Lipid Class Used for Omega-3 Fatty Acid Supplementation on Liver Fat Accumulation in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.

Postprandial exercise regulates tissue-specific triglyceride uptake through angiopoietin-like proteins.

Fuel substrate switching between carbohydrates and fat is essential for maintaining metabolic homeostasis. During aerobic exercise, the predominant energy source gradually shifts from carbohydrates to fat. While it is well known that exercise mobilizes fat storage from adipose tissues, it remains largely obscure how circulating lipids are distributed tissue-specifically according to distinct energy requirements. Here, we demonstrate that aerobic exercise is linked to nutrient availability to regulate tissue-specific activities of lipoprotein lipase (LPL), the key enzyme catabolizing circulating triglyceride (TG) for tissue uptake, through the differential actions of angiopoietin-like (ANGPTL) proteins. Exercise reduced the tissue binding of ANGPTL3 protein, increasing LPL activity and TG uptake in the heart and skeletal muscle in the postprandial state specifically. Mechanistically, exercise suppressed insulin secretion, attenuating hepatic Angptl8 transcription through the PI3K/mTOR/CEBPα pathway, which is imperative for the tissue binding of its partner ANGPTL3. Constitutive expression of ANGPTL8 hampered lipid utilization and resulted in cardiac dysfunction in response to exercise. Conversely, exercise promoted the expression of ANGPTL4 in white adipose tissues, overriding the regulatory actions of ANGPTL8/ANGPTL3 in suppressing adipose LPL activity, thereby diverting circulating TG away from storage. Collectively, our findings show an overlooked bifurcated ANGPTL-LPL network that orchestrates fuel switching in response to aerobic exercise.