Body Energy Metabolism Research Articles

Evodiamine promotes differentiation and inhibits proliferation of C2C12 muscle cells.

Evodiamine is a botanical alkaloid compound extracted from Tetradium plants. Previous studies have reported that evodiamine (Evo) treatment can reduce food uptake and improve insulin resistance in animals . The skeletal muscle comprises about 40% of the body mass of adults and has a vital role in regulating whole body glucose metabolism and energy metabolism. However, the effect of Evo on skeletal muscle is unclear. The main aim of the present study was to investigate the effect of Evo on the differentiation and proliferation of the mouse C2C12 muscle cell line. The results demonstrated that Evo promoted the expression of myogenic marker genes (Myogenin and muscle myosin heavy chain) and increased myoblast differentiation, potentially via activation of the Wnt/β‑catenin pathway. Furthermore, Evo increased mRNA expression of p21, reduced mRNA expression of CyclinB, CyclinD and CyclinE and reduced the percentage of proliferating cells. Also, phosphorylation of ERK1/2 was decreased by Evo treatment during cell proliferation. In conclusion, these findings indicated that Evo has marked effects on skeletal muscle development.

Generation and phenotypic characterisation of a cytochrome P450 4x1 knockout mouse.

Cytochrome P450 4x1 (Cyp4x1) is expressed at very high levels in the brain but the function of this protein is unknown. It has been hypothesised to regulate metabolism of fatty acids and to affect the activity of endocannabinoid signalling systems, which are known to influence appetite and energy metabolism. The objective of the present investigation was to determine the impact of Cyp4x1 on body weight and energy metabolism by developing a line of transgenic Cyp4x1-knock out mice. Mice were developed with a global knock-out of the gene; the full-length RNA was undetectable, and mice were viable and fertile. Both male and female Cyp4x1-knock out mice gained significantly more body weight on normal lab chow diet compared to control flox mice on the same genetic background. At necropsy, Cyp4x1-knock out male mice had significantly greater intra-abdominal fat deposits (P<0.01), and enlarged adipocytes. Metabolic rate and locomotor activity as inferred from VO2 measures and crossing of infrared beams in metabolic cages were not significantly affected by the mutation in either gender. The respiratory exchange ratio was significantly decreased in male knock out mice (P<0.05), suggesting a greater degree of fat oxidation, consistent with their higher adiposity. When mice were maintained on a high fat diet, VO2 was significantly decreased in both male and female Cyp4x1-knock out mice. We conclude that the Cyp4x1-knock out mouse strain demonstrates a mildly obese phenotype, consistent with the view that cytochrome P450 4x1 plays a role in regulating fat metabolism.

Linking Metabolic Disease With the PGC-1α Gly482Ser Polymorphism.

Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is a highly conserved transcriptional coactivator enriched in metabolically active tissues including liver, adipose, pancreas, and muscle. It plays a role in regulating whole body energy metabolism and its deregulation has been implicated in type 2 diabetes (T2D). A single nucleotide variant of the PPARGC1A gene (rs8192678) is associated with T2D susceptibility, relative risk of obesity and insulin resistance, and lower indices of β cell function. This common polymorphism is within a highly conserved region of the bioactive protein and leads to a single amino acid substitution (glycine 482 to serine). Its prevalence and effects on metabolic parameters appear to vary depending on factors including ethnicity and sex, suggesting important interactions between genetics and cultural/environmental factors and associated disease risk. Interestingly, carriers of the serine allele respond better to some T2D interventions, illustrating the importance of understanding functional impacts of genetic variance on PGC-1α when targeting this pathway for personalized medicine. This review summarizes a growing body of literature surrounding possible links between the PGC-1α Gly482Ser single nucleotide polymorphism and diabetes, with focus on key clinical findings, affected metabolic systems, potential molecular mechanisms, and the influence of geographical or ethnic background on associated risk.

Cadm2 regulates body weight and energy homeostasis in mice

ObjectiveObesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain. MethodsWe first analyzed Cadm2 expression in the brain of both human subjects and mouse models and subsequently characterized a loss-of-function mouse model of Cadm2 for alterations in glucose and energy homeostasis. ResultsWe show that the risk variant rs13078960 associates with increased CADM2 expression in the hypothalamus of human subjects. Increased Cadm2 expression in several brain regions of Lepob/ob mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese mice (Cadm2/ob) resulted in reduced adiposity, systemic glucose levels, and improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor activity, energy expenditure rate, and core body temperature identifying Cadm2 as a potent regulator of systemic energy homeostasis. ConclusionsTogether these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis.

Chronic subcutaneous infusion of neurosecretory protein GM increases body mass gain in chicks

Recently we discovered a small hypothalamic protein in the chicken, named neurosecretory protein GL (NPGL), which is associated with body growth and energy metabolism in birds and rodents. Genome database analysis suggested that the NPGL gene has a paralogous gene in vertebrates, named neurosecretory protein GM (NPGM). However, the biological action of NPGM remains unclear. In this study, we investigated whether NPGM affects body growth in chicks. We found that subcutaneous infusion of NPGM for six days increased body mass gain in a dose-dependent manner. Despite the observed increase in body mass, infusion of NPGM did not alter food and water intake. Of note, we observed tendency of mass increase of several peripheral tissues, specifically. When we compared several tissue types, NPGM seemed to induce the largest growth increase in white adipose tissue mass. These results suggest that NPGM may accelerate fat accumulation and body growth. In addition, we analyzed whether NPGM increases body growth through the action of pituitary hormones. However, we observed no significant changes in mRNA expression of pituitary hormones or plasma levels of growth hormone in NPGM-treated chicks. This is the first report describing the biological action of NPGM in vertebrates.

Performance, body fat reserves and plasma metabolites in Brown Swiss dairy cows: Indoor feeding versus pasture-based feeding.

Feeding dairy cows indoors or on pasture affects not only labour, machinery and housing costs, but also animals' performance and metabolism. This study investigates the effects of indoor feeding (IF) with a partial-mixed ration (PMR) versus pasture-based feeding (PF) on milk production, fertility, backfat thickness (BFT), body weight (BW) loss and energy metabolism of Brown Swiss (BS) dairy cows with similar genetic production potential. The IF herd consisted of 13 cows fed a PMR composed of maize and grass silage plus protein concentrate according to each cow's requirements. The PF herd consisted of 14cows offered barn-ventilated hay ad libitum after calving from January until March and grazed on semi-continuous pastures during the vegetation period. The IF cows produced more energy-corrected milk (ECM) per standard lactation (9,407 vs. 5,960kg; p<.01), more milk fat (378 vs. 227kg; p<.01) and milk protein (326 vs. 215kg; p<.01). The calving interval (377 vs. 405days; p<.01) and time empty (86 vs. 118 days; p<.01) were shorter in the PF compared to IF, possibly also due to different selection criteria for maintaining the respective seasonal calving rhythm. The empty body fat loss calculated according to BCS until its nadir was higher in IF cows (IF: 10.4 vs. PF: 4.8 MJ/day; p<.01), but no differences were noted in total body fat loss estimated via BFT (p=.24). However, PF had lower blood glucose concentration at all investigated time points, but no differences occurred in serum non-esterified fatty acid and β-hydroxybutyrate concentrations post-partum. In conclusion, BS cows were equally well suited for the IF with PMR and the PF system investigated here without developing a prominent metabolic load despite differences in nutrient supply. As such, investigated BS dairy cows in our trial seem to have a high capacity for metabolic adaptation to different production systems.

The effects of ovariectomy and lifelong high-fat diet consumption on body weight, appetite, and lifespan in female rats

In females, ovarian hormones play pivotal roles in metabolic, appetite, and body weight regulation. In addition, it has been reported that ovarian hormones also affect longevity in some species. Recently, it was found that the consumption of a high-fat diet aggravates ovariectomy-associated metabolic dysregulation in female rodents. The aim of this study was to investigate the hypothesis that long-term high-fat diet consumption and ovariectomy interact to worsen body weight regulation and longevity in female rats.At 21days of age, female rats were weaned and randomly divided into two groups, one of which was given the high-fat diet, and the other was supplied with standard chow. At 23weeks of age, each group was further divided into ovariectomized and sham-operated groups, and then their body weight changes, food intake, and longevity were measured until 34months of age. The sham – high-fat diet rats exhibited greater body weight changes and higher feed efficiency than the sham – standard chow rats. On the other hand, the ovariectomized – high-fat diet and ovariectomized - standard chow rats displayed similar body weight changes and feed efficiency. The sham – high-fat diet and ovariectomized – standard chow rats demonstrated similar body weight changes and feed efficiency, indicating that the impact of ovariectomy on the regulation of body weight and energy metabolism might be similar to that of high-fat diet. Contrary to our expectations, ovariectomy and high-fat diet consumption both had small favorable effects on longevity. As the high-fat diet used in the present study not only had a high fat content, but also had a high caloric content and a low carbohydrate content compared with the standard chow, it is possible that the effects of the high-fat diet on body weight and longevity were partially induced by its caloric/carbohydrate contents. These findings indicate that the alterations in body weight and energy metabolism induced by ovariectomy and high-fat diet might not directly affect the lifespan of female rats.

Front cover: Cyanidin‐3‐glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

Front cover: Cyanidin‐3‐glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

The Microbiome That Shapes Us: Can It Cause Obesity?

We sought to examine the effects of the gut microbial makeup on weight gain and obesity. We wanted to find out what the current research on this topic was and what the effect of the gut microbiota on energy metabolism is, as well the effects of diet on the microbiome and what effect the microbiome has on metabolic syndrome. Obesity is thought to be due to greater calorie intake than expenditure. Recently, research has looked into the effects of the microbiome on obesity. Our gut flora is made up of trillions of microbes and there is evidence to suggest that even from the earliest stages of life, altering that flora can affect human's ability to gain and lose weight, which can lead to obesity and ultimately other disease such as cardiovascular disease, diabetes mellitus, and liver disease. Obesity can affect the human body in profound ways and lead to a multitude of comorbidities. We found that the obesity pandemic appears to parallel the increased use of antibiotics seen across the US. In addition, the use of antibiotics can alter the gut flora even from the earliest stages of life and the altered microbiome can alter our body habitus and energy metabolism through antibiotics, diet, and bariatric surgery.

Genetic inhibition of PPARγ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis

A common feature of many skeletal diseases is the accumulation of marrow fat. A reciprocal relationship exists between osteogenesis and adipogenesis in bone marrow that is mediated by the relative activity of PPARγ and RUNX2 transcription factors. The ERK/MAPK pathway is an important inducer of MSC differentiation to osteoblasts and an inhibitor of adipogenesis that functions by phosphorylating RUNX2 and PPARγ. To begin to assess the importance of this regulation in vivo, we examined the consequences of blocking one arm of this pathway, PPARγ S112 phosphorylation, by evaluating the bone phenotype of PPARγ S112A mutant mice. This mutation prevents MAPK phosphorylation and inhibition of PPARγ transcriptional activity. Both male and female PPARγ S112A mice had decreased tibial and vertebral BV/TV and decreased trabecular bone relative to wild type littermates. These results were explained by a decrease in bone formation and osteoblast activity in the absence of changes in resorption. In contrast, marrow adipose tissue, adipocyte markers and serum adiponectin were all dramatically increased. Bone marrow stromal cells isolated from PPARγ S112A mice had elevated PPARγ and preferentially differentiated to adipocytes while total and phosphorylated RUNX2 and osteoblastogenesis were inhibited, indicating that the PPARγ S112A mutation affects bone in a cell autonomous manner. Changes in osteoblast/adipocyte lineage allocation in MSC cultures were also seen where CFU-OBs were reduced with a parallel increase in CFU-AD. This study emphasizes the importance of PPARγ phosphorylation in controlling bone mass and marrow adiposity and demonstrates how a regulatory mutation in PPARγ previously associated with peripheral fat metabolism can have broader effects on bone homeostasis that may in turn affect whole body energy metabolism.

Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

ObjectivesDioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life.Study designIn The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS.ResultsPrenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI.Discussion/ConclusionThis study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

Determinación de fosfatos de adenosina en sangre de pacientes hepáticos

Adenosine phosphates play an important role in the body's energy metabolism. Tissues in intense physiological activity, such as muscle tissue, nervous tissue, renal tubules, etc., according to research by Palladin Bing, and others, are tissues rich in adenosine triphosphate (ATP).

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function.

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue (BAT) formation and function increases energy expenditure and may protect against obesity. Cyanidin-3-glucoside (C3G) is an anthocyanin compound that occurs naturally in many fruits and vegetables. In this study, we investigated the effect and mechanism of C3G on the prevention of obesity. Db/db mice received C3G dissolved in drinking water for 16 wk; drinking water served as the vehicle treatment. The total body weight, energy intake, metabolic rate, and physical activity were measured. The lipid droplets, gene expression and protein expression were evaluated by histochemical staining, real-time PCR, and western blots. We found that C3G increased energy expenditure, limited weight gain, maintained glucose homeostasis, reversed hepatic steatosis, improved cold tolerance, and enhanced BAT activity in obese db/db mice. C3G also induces brown-like adipocytes (beige) formation in subcutaneous white adipose tissue (sWAT) of db/db mice model. We also found that C3G potently regulates the transcription of uncoupling protein 1 (UCP1) both in BAT and sWAT through increasing mitochondrial number and function. Our results suggest that C3G plays a role in regulating systemic energy balance, which may have potential therapeutic implications for the prevention and control of obesity.

Epigenetic Regulation of Adipokines

Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

Metabolic phenotype in the mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2 Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O2 consumption and CO2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin.

Adipose tissue and liver.

Adipose tissue and liver are central tissues in whole body energy metabolism. Their composition, structure, and function can be noninvasively imaged using a variety of measurement techniques that provide a safe alternative to an invasive biopsy. Imaging of adipose tissue is focused on quantitating the distribution of adipose tissue in subcutaneous and intra-abdominal (visceral) adipose tissue depots. Also, detailed subdivisions of adipose tissue can be distinguished with modern imaging techniques. Adipose tissue (or adipocyte) accumulation or infiltration of other organs can also be imaged, with intramuscular adipose tissue a common example. Although liver fat content is now accurately imaged using standard magnetic resonance imaging (MRI) techniques, inflammation and fibrosis are more difficult to determine noninvasively. Liver imaging efforts are therefore concerted on developing accurate imaging markers of liver fibrosis and inflammatory status. Magnetic resonance elastography (MRE) is presently the most reliable imaging technique for measuring liver fibrosis but requires an external device for introduction of shear waves to the liver. Methods using multiparametric diffusion, perfusion, relaxometry, and hepatocyte-specific MRI contrast agents may prove to be more easily implemented by clinicians, provided they reach similar accuracy as MRE. Adipose tissue imaging is experiencing a revolution with renewed interest in characterizing and identifying distinct adipose depots, among them brown adipose tissue. Magnetic resonance spectroscopy provides an interesting yet underutilized way of imaging adipose tissue metabolism through its fatty acid composition. Further studies may shed light on the role of fatty acid composition in different depots and why saturated fat in subcutaneous adipose tissue is a marker of high insulin sensitivity.

Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory

Efficient energy use has constrained the evolution of nervous systems. However, it is unresolved whether energy metabolism may resultantly regulate major brain functions. Our observation that Drosophila flies double their sucrose intake at an early stage of long-term memory formation initiated the investigation of how energy metabolism intervenes in this process. Cellular-resolution imaging of energy metabolism reveals a concurrent elevation of energy consumption in neurons of the mushroom body, the fly’s major memory centre. Strikingly, upregulation of mushroom body energy flux is both necessary and sufficient to drive long-term memory formation. This effect is triggered by a specific pair of dopaminergic neurons afferent to the mushroom bodies, via the D5-like DAMB dopamine receptor. Hence, dopamine signalling mediates an energy switch in the mushroom body that controls long-term memory encoding. Our data thus point to an instructional role for energy flux in the execution of demanding higher brain functions.

Brown adipose tissue and lipid metabolism imaging.

Brown adipose tissue (BAT) research has evolved from an underestimated to a fast developing field. Its assumed curing properties for the world wide epidemic obesity, and its related diseases, makes this tissue an interesting target for a broad amount of non-invasive molecular BAT tracers. Apart from 18F-FDG PET/CT there are several methods to detect BAT and measure its metabolism in a more appropriate way. Especially interesting is the measure of lipid turnover, because fatty acids comprise the main fuel for active BAT. This review outlines different imaging modalities suitable for BAT imaging with the overall goal to explain the yet not completely understood mechanism in BAT and its quantitative contribution to whole body lipid and energy metabolism. Publications with focus on brown adipose tissue and lipid metabolism imaging are analyzed, different imaging approaches are introduced and promising BAT tracers are presented. Radiolabelled and fluorescent fatty acids, labelled particles, 3H-Triolein and ADIFAB staining can give information about the inflow and therefore about the utilization of fatty acids which represents the activation state in vivo/in vitro. Non-invasive scanning with CT or MRI is a useful addition to those techniques. Lipid metabolism imaging offers the opportunity to visualize and quantify yet undiscovered aspects of BAT metabolic activities and is key to completely clarify its role in whole body lipid and energy metabolism.

Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells

BackgroundVitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Material and methodsWhole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XFe96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method. Results25(OH)D increased by a median (IQR) of 14.40 (20.13)nmol/L (p<0.001) from winter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (<50nmol/L), had the greatest alteration in bioenergetic parameters in summer, relative to those with winter 25(OH)D concentrations of 50–75nmol/L or >75nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics. ConclusionSeasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants confirmation through cause and effect study designs.

Phospholipase C-related catalytically inactive protein-knockout mice exhibit uncoupling protein 1 upregulation in adipose tissues following chronic cold exposure

ObjectivesWe have previously demonstrated that phospholipase C-related catalytically inactive protein (PRIP) is involved in fat metabolism and energy consumption. However, whether PRIP participates in body energy metabolism in vivo remains to be determined. Therefore, we examined whether PRIP deficiency affects whole-body energy homeostasis, which is modulated by non-shivering thermogenesis in brown adipose tissue, using a cold exposure animal model. MethodsFasting plasma triacylglycerol levels were measured to evaluate fat metabolism in wild-type and Prip-KO mice. In addition, a glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. To determine changes in energy consumption, mice were exposed to a cold environment for 7 days, and expression of uncoupling protein 1 (UCP1) in brown adipose tissue was analyzed via western blotting. ResultsFasting plasma levels of triacylglycerols were significantly higher in Prip-KO mice than in wild-type mice. However, Prip-KO mice showed a healthy phenotype based on GTT and ITT. UCP1 expression was significantly upregulated in the brown and white adipose tissues of Prip-KO mice exposed to cold conditions. ConclusionPrip-KO mice exhibit greater ability to consume lipids as an energy source, indicating that PRIP modulates of systemic energy expenditure. Our findings provide increased understanding of PRIP-mediated non-shivering thermogenic mechanisms and offers important insights for the treatment and control of obesity.