RESUMEN
AIMS: We explored the early effects of bariatric surgery on subclinical myocardial function in individuals with severe obesity and preserved left ventricular (LV) ejection fraction. METHODS: Thirty-eight patients with severe obesity [body mass index (BMI) ≥35â¯kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) (Surgery group), 19 patients with severe obesity managed with usual care (Medical group), and 18 age and sex-matched non-obese controls (non-obese group) were included. Left ventricular global longitudinal strain (LV GLS) was evaluated with echocardiography speckle tracking imaging. Abnormal myocardial function was defined as LV GLS <18%. RESULTS: Age of the participants was 42⯱â¯11â¯years with a BMI of 48⯱â¯8â¯kg/m2 (mean⯱â¯standard deviation); 82% were female. The percentage of total weight loss at 6â¯months after bariatric surgery was 26.3⯱â¯5.2%. Proportions of hypertension (61 vs. 30%, Pâ¯=â¯0.0005), dyslipidemia (42 vs. 5%, Pâ¯=â¯0.0001) and type 2 diabetes (40 vs. 13%, Pâ¯=â¯0.002) were reduced postoperatively. Before surgery, patients with obesity displayed abnormal subclinical myocardial function vs. non-obese controls (LV GLS, 16.3⯱â¯2.5 vs. 19.6⯱â¯1.7%, Pâ¯<â¯0.001). Six months after bariatric surgery, the subclinical myocardial function was comparable to non-obese (LV GLS, 18.2⯱â¯1.9 vs. 19.6⯱â¯1.7%, surgery vs. non-obese, Pâ¯=â¯NS). On the contrary, half of individuals with obesity managed medically worsened their myocardial function during the follow-up (Pâ¯=â¯0.002). Improvement in subclinical myocardial function following bariatric surgery was associated with changes in abdominal visceral fat (râ¯=â¯0.43, Pâ¯<â¯0.05) and inflammatory markers (râ¯=â¯0.45, Pâ¯<â¯0.01), whereas no significant association was found with weight loss or change in insulin sensitivity (HOMA-IR) (Pâ¯>â¯0.05). In a multivariate model, losing visceral fat mass was independently associated with improved subclinical myocardial function. CONCLUSIONS: Bariatric surgery was associated with significant improvement in the metabolic profile and in subclinical myocardial function. Early improvement in subclinical myocardial function following bariatric surgery was related to a greater mobilization of visceral fat depot, linked to global fat dysfunction and cardiometabolic morbidity.
Asunto(s)
Cirugía Bariátrica , Movilización Lipídica/fisiología , Obesidad Mórbida/cirugía , Función Ventricular Izquierda/fisiología , Adulto , Enfermedades Asintomáticas , Estudios de Casos y Controles , Ecocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Grasa Intraabdominal/metabolismo , Masculino , Persona de Mediana Edad , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/metabolismo , Obesidad Mórbida/fisiopatología , Periodo Posoperatorio , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Individuals with postnatal growth retardation (PGR) are prone to developing chronic disease. Abnormal development in small intestine is casually implicated in impaired growth performance. However, the exact mechanism is still unknown. In this present study, PGR piglets (aged 42 days) were employed as a good model to analyse changes in nutrient absorption and energy metabolism in the intestinal mucosa. The results showed lower serum concentrations of free amino acids, and lipid metabolites in PGR piglets, which were in accordance with the down-regulated mRNA expressions involved in fatty acid and amino acid transporters in the jejunal and ileal mucosa. The decreased activities of digestive enzymes and the marked swelling in mitochondria were also observed in the PGR piglets. In addition, it was found that lower ATP production, higher AMP/ATP ratio, deteriorated mitochondrial complex III and ATP synthase, and decreased manganese superoxide dismutase activity in the intestinal mucosa of PGR piglets. Furthermore, altered gene expression involved in energy metabolism, accompanied by decreases in the protein abundance of SIRT1, PGC-1α and PPARγ, as well as phosphorylations of AMPKα, mTOR, P70S6K and 4E-BP1 were observed in intestinal mucosa of PGR piglets. In conclusion, decreased capability of nutrient absorption, mitochondrial dysfunction, and aberrant energy status in the jejunal and ileal mucosa may contribute to PGR piglets.
Asunto(s)
Metabolismo Energético/fisiología , Retardo del Crecimiento Fetal/metabolismo , Mucosa Intestinal/metabolismo , Mitocondrias/metabolismo , Adenosina Monofosfato/metabolismo , Adenosina Trifosfato/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/metabolismo , Animales , Regulación hacia Abajo/fisiología , Ácidos Grasos/metabolismo , Íleon/metabolismo , Yeyuno/metabolismo , Movilización Lipídica/fisiología , Masculino , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Fosforilación/fisiología , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismo , PorcinosRESUMEN
Little is known about the influence of central nesfatin-1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin-1 regulates lipid metabolism in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high-fat diets (HFDs) and were treated twice with low-dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin-1 required the hypothalamic-sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP-activated protein kinase (AMPK) levels in skeletal muscle and hormone-sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin-1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin-1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty-acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin-1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin-1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.
Asunto(s)
Tejido Adiposo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Ácidos Grasos/metabolismo , Movilización Lipídica/fisiología , Nucleobindinas/metabolismo , Sistema Nervioso Simpático/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Músculo EsqueléticoRESUMEN
Mice homozygous for the human GRACILE syndrome mutation (Bcs1lc.A232G) display decreased respiratory chain complex III activity, liver dysfunction, hypoglycemia, rapid loss of white adipose tissue and early death. To assess the underlying mechanism of the lipodystrophy in homozygous mice (Bcs1lp.S78G), these and wild-type control mice were subjected to a short 4-hour fast. The homozygotes had low baseline blood glucose values, but a similar decrease in response to fasting as in wild-type mice, resulting in hypoglycemia in the majority. Despite the already depleted glycogen and increased triacylglycerol content in the mutant livers, the mice responded to fasting by further depletion and increase, respectively. Increased plasma free fatty acids (FAs) upon fasting suggested normal capacity for mobilization of lipids from white adipose tissue into circulation. Strikingly, however, serum glycerol concentration was not increased concomitantly with free FAs, suggesting its rapid uptake into the liver and utilization for fuel or gluconeogenesis in the mutants. The mutant hepatocyte mitochondria were capable of responding to fasting by appropriate morphological changes, as analyzed by electron microscopy, and by increasing respiration. Mutants showed increased hepatic gene expression of major metabolic controllers typically associated with fasting response (Ppargc1a, Fgf21, Cd36) already in the fed state, suggesting a chronic starvation-like metabolic condition. Despite this, the mutant mice responded largely normally to fasting by increasing hepatic respiration and switching to FA utilization, indicating that the mechanisms driving these adaptations are not compromised by the CIII dysfunction. SUMMARY STATEMENT: Bcs1l mutant mice with severe CIII deficiency, energy deprivation and post-weaning lipolysis respond to fasting similarly to wild-type mice, suggesting largely normal systemic lipid mobilization and utilization mechanisms.
Asunto(s)
Complejo III de Transporte de Electrones/metabolismo , Ayuno/fisiología , Movilización Lipídica/fisiología , Acidosis Láctica/metabolismo , Animales , Glucemia/metabolismo , Colestasis/metabolismo , Transporte de Electrón/fisiología , Femenino , Retardo del Crecimiento Fetal/metabolismo , Gluconeogénesis/fisiología , Glucógeno/metabolismo , Hemosiderosis/metabolismo , Hepatocitos/metabolismo , Hepatocitos/fisiología , Homocigoto , Hipoglucemia/metabolismo , Hipoglucemia/fisiopatología , Hígado/metabolismo , Hígado/fisiología , Masculino , Errores Innatos del Metabolismo/metabolismo , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/fisiología , Enfermedades Mitocondriales/congénito , Enfermedades Mitocondriales/metabolismo , Aminoacidurias Renales/metabolismo , Triglicéridos/metabolismoRESUMEN
Fetuin-A (FetA) is an adipokine and free fatty acid (FFA) carrier linked to adipose tissue (AT) function in monogastrics and ruminants. In dairy cows, plasma and AT FetA decrease after parturition, coinciding with reduced lipogenesis and increased lipolysis. In monogastrics, FetA enhances lipogenesis, but its role on lipid mobilization of ruminants is unclear. We hypothesized that FetA modulates lipid mobilization in bovine AT by enhancing the lipogenic activity of adipocytes. Our objective was to determine the effects of FetA on lipogenesis and lipolysis in cultured primary adipocytes from dairy cows. Preadipocytes from the tailhead subcutaneous AT depot were induced to differentiate in a 7-d coculture in vitro model. The effects of FetA on lipolytic responses of adipocytes were evaluated after a 2-h ß-adrenergic stimulation with 1 µM isoproterenol (ISO) alone or combined with 0.1 mg/mL of FetA (FetA+ISO), and in cells treated with medium alone (CON) or with 0.1 mg/mL of FetA (FetA). Lipogenic responses of adipocytes treated with CON or FetA from d 5 to 7 of differentiation were assessed by fatty acid (FA) uptake quantification and triacylglycerol (TAG) accumulation, and the gene and protein expression of lipogenic markers. Bovine adipocytes abundantly expressed FetA gene and protein and secreted 48 ± 3.5 ng/DNA relative fluorescence units (RFU). Adrenergic stimulation with ISO increased lipolysis compared with CON, as reflected in the release of glycerol (0.12 ± 0.04 vs. 0.04 ± 0.02 nM/DNA RFU) and FFA (15 ± 13 vs. 6.2 ± 2.4 nM/DNA RFU). Lipolysis induced by ISO was attenuated by the addition of FetA (FetA+ISO) as reflected by lower glycerol (0.06 ± 0.04 nM/DNA RFU) and FFA (5.7 ± 2.7 nM/DNA RFU) release compared with ISO alone. Compared with CON, FetA enhanced lipogenic responses as demonstrated by higher FA uptake and increased accumulation of TAG. Exposure to FetA upregulated 1-acylglycerol-3-phosphate acyltransferase-2 (AGPAT2) gene expression and protein content, as well as its activity. Adipocytes exposed to FetA increased the secretion of the metabolite of AGPAT2, phosphatidic acid. In conclusion, FetA attenuates lipolytic responses and enhances lipogenesis in bovine adipocytes. The upregulation of the rate-limiting lipogenic enzyme AGPAT2 by FetA suggests a potential pathway by which this adipokine promotes TAG synthesis in adipocytes. These findings suggest that FetA is a potential target for lipid mobilization modulation in AT of dairy cows.
Asunto(s)
Bovinos/fisiología , Regulación de la Expresión Génica , Lipogénesis/fisiología , Lipólisis/fisiología , alfa-2-Glicoproteína-HS/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Ácidos Grasos no Esterificados/metabolismo , Femenino , Isoproterenol/farmacología , Movilización Lipídica/fisiología , Parto , Embarazo , Grasa Subcutánea/efectos de los fármacos , Grasa Subcutánea/metabolismo , Triglicéridos/metabolismoRESUMEN
Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well-characterized autophagy-related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood. Here, we have applied sensitized pooled CRISPR screens and identify the uncharacterized transmembrane protein TMEM41B as a novel regulator of autophagy. In the absence of TMEM41B, autophagosome biogenesis is stalled, LC3 accumulates at WIPI2- and DFCP1-positive isolation membranes, and lysosomal flux of autophagy cargo receptors and intracellular bacteria is impaired. In addition to defective autophagy, TMEM41B knockout cells display significantly enlarged lipid droplets and reduced mobilization and ß-oxidation of fatty acids. Immunostaining and interaction proteomics data suggest that TMEM41B localizes to the endoplasmic reticulum (ER). Taken together, we propose that TMEM41B is a novel ER-localized regulator of autophagosome biogenesis and lipid mobilization.
Asunto(s)
Autofagia/fisiología , Movilización Lipídica/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Autofagosomas/metabolismo , Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Proteína 9 Asociada a CRISPR/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/fisiología , Retículo Endoplásmico/metabolismo , Ácidos Grasos/metabolismo , Técnicas de Inactivación de Genes , Células HeLa , Homeostasis , Humanos , Lentivirus , Gotas Lipídicas/metabolismo , Movilización Lipídica/genética , Lisosomas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismoRESUMEN
Lipid droplets (LDs) have well-established functions as sites for lipid storage and energy mobilization to meet the metabolic demands of cells. However, recent studies have expanded the roles of LDs to protein quality control. Lipophagy, or LD degradation by autophagy, plays a vital role not only in the mobilization of free fatty acids (FFAs) and lipid homeostasis at LDs, but also in the adaptation of cells to certain forms of stress including lipid imbalance. Recent studies have provided new mechanistic insights about the diverse types of lipophagy, in particular microlipophagy. This review summarizes key findings about the mechanisms and functions of lipophagy and highlights a novel function of LD microlipophagy as a mechanism to maintain endoplasmic reticulum (ER) proteostasis under conditions of lipid imbalance.
Asunto(s)
Autofagia/fisiología , Homeostasis/fisiología , Gotas Lipídicas/metabolismo , Movilización Lipídica/fisiología , Animales , Retículo Endoplásmico/metabolismo , Humanos , Metabolismo de los Lípidos/fisiología , Proteostasis/fisiologíaRESUMEN
Fatty acid-binding protein 4 (FABP4), a cytosolic lipid chaperone predominantly expressed in adipocytes and macrophages, modulates lipid fluxes, trafficking, signaling, and metabolism. Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis. However, the role of FABP4 in bacterial infection, metabolic crosstalk between host and pathogen, and bacterial pathogenesis have not been studied. As an obligate intracellular pathogen, Chlamydia pneumoniae needs to obtain nutrients such as ATP and lipids from host cells. Here, we show that C. pneumoniae successfully infects and proliferates in murine adipocytes by inducing hormone sensitive lipase (HSL)-mediated lipolysis. Chemical inhibition or genetic manipulation of HSL significantly abrogated the intracellular growth of C. pneumoniae in adipocytes. Liberated free fatty acids were utilized to generate ATP via ß-oxidation, which C. pneumoniae usurped for its replication. Strikingly, chemical inhibition or genetic silencing of FABP4 significantly abrogated C. pneumoniae infection-induced lipolysis and mobilization of liberated FFAs, resulting in reduced bacterial growth in adipocytes. Collectively, these results demonstrate that C. pneumoniae exploits host FABP4 to facilitate fat mobilization and intracellular replication in adipocytes. This work uncovers a novel strategy used by intracellular pathogens for acquiring energy via hijacking of the host lipid metabolism pathway.
Asunto(s)
Adipocitos/microbiología , Adipocitos/fisiología , Chlamydophila pneumoniae/fisiología , Proteínas de Unión a Ácidos Grasos/metabolismo , Movilización Lipídica/fisiología , Esterol Esterasa/metabolismo , Células 3T3-L1 , Animales , Proliferación Celular/fisiología , Chlamydophila pneumoniae/citología , RatonesRESUMEN
Aggression can benefit individuals by enhancing their dominance and thereby their ability to acquire and retain resources that increase survival or fitness. Engaging in aggressive behavior costs energy and how animals manage their energy budget to accommodate aggression remains unclear. We conducted three experiments to examine changes in physiological, behavioral and hormonal markers indicative of energy budget in male striped hamsters subject to resident-intruder aggression tests. Body temperature, metabolic rate and serum corticosterone levels significantly increased in resident hamsters immediately after the introduction of intruders. Energy intake did not change, but the metabolic rate of residents increased by 16.1% after 42-days of repeated encounters with intruders. Residents had significantly decreased body fat content and serum thyroxine (T4) levels, and a considerably elevated tri-iodothyronine (T3)/T4 ratio compared to a control group that had no intruders. Attack latency considerably shortened, and the number of attack bouts and total duration of attacks, significantly increased in residents on day 42 compared to day 1 of experiments. These findings may suggest that the conversion of T4 to T3 is involved in defensive aggression behavior. The mobilization of fat reserves resulting in lean body mass is probably common response to the increased metabolic cost of aggression in small mammals. Aggressive behavior, which is important for the successful acquisition and defense of resources, may be of significance for adaptation and evolution of metabolic rate.
Asunto(s)
Tejido Adiposo/metabolismo , Agresión/fisiología , Metabolismo Energético/fisiología , Lipólisis/fisiología , Animales , Conducta Animal/fisiología , Temperatura Corporal/fisiología , Corticosterona/sangre , Cricetinae , Ingestión de Energía/fisiología , Movilización Lipídica/fisiología , Masculino , Consumo de Oxígeno/fisiología , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
AIMS/HYPOTHESIS: Dysfunction of lipid metabolism in white adipose tissue can substantially interfere with health and quality of life, for example in obesity and associated metabolic diseases. Therefore, it is important to characterise pathways that regulate lipid handling in adipocytes and determine how they affect metabolic homeostasis. Components of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway are involved in adipocyte physiology and pathophysiology. However, the exact physiological importance of the STAT family member STAT5 in white adipose tissue is yet to be determined. Here, we aimed to delineate adipocyte STAT5 functions in the context of lipid metabolism in white adipose tissue. METHODS: We generated an adipocyte specific knockout of Stat5 in mice using the Adipoq-Cre recombinase transgene followed by in vivo and in vitro biochemical and molecular studies. RESULTS: Adipocyte-specific deletion of Stat5 resulted in increased adiposity, while insulin resistance and gluconeogenic capacity was decreased, indicating that glucose metabolism can be improved by interfering with adipose STAT5 function. Basal lipolysis and fasting-induced lipid mobilisation were diminished upon STAT5 deficiency, which coincided with reduced levels of the rate-limiting lipase of triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL, encoded by Pnpla2) and its coactivator comparative gene identification 58 (CGI-58). In a mechanistic analysis, we identified a functional STAT5 response element within the Pnpla2 promoter, indicating that Pnpla2 is transcriptionally regulated by STAT5. CONCLUSIONS/INTERPRETATION: Our findings reveal an essential role for STAT5 in maintaining lipid homeostasis in white adipose tissue and provide a rationale for future studies into the potential of STAT5 manipulation to improve outcomes in metabolic diseases.
Asunto(s)
Adipocitos/metabolismo , Adiposidad/fisiología , Factor de Transcripción STAT5/metabolismo , Células 3T3-L1 , Adiposidad/genética , Animales , Western Blotting , Inmunoprecipitación de Cromatina , Ensayo de Cambio de Movilidad Electroforética , Femenino , Glucosa/metabolismo , Resistencia a la Insulina/genética , Resistencia a la Insulina/fisiología , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Movilización Lipídica/genética , Movilización Lipídica/fisiología , Lipólisis/genética , Lipólisis/fisiología , Masculino , Ratones , Calidad de Vida , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción STAT5/genéticaRESUMEN
Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
Asunto(s)
Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos/fisiología , Lipólisis/fisiología , Animales , Homeostasis/genética , Humanos , Movilización Lipídica/fisiología , Redes y Vías Metabólicas/genéticaRESUMEN
Heat stress is a major factor contributing to low fertility of dairy cows with a great economic impact in dairy industry. Heat-stressed dairy cows usually have reduced nutrient intake, resulting in a higher degree of negative energy balance (NEB). The aim of this study was to investigate the seasonal thermal effect on lipid metabolism, antioxidant activity and reproductive performance in dairy cows. Thirty-two healthy dairy heifers were included in the study. According to the ambient temperature, animals were divided into two groups: winter (N = 14) and summer season (N = 18). Metabolic parameters, paraoxonase-1 (PON1) activity and total antioxidant status (TAS) were monitored at the time of insemination (basal values) and from 1 week before until 8 weeks after calving. Number of services per conception and calving-to-conception (CC) interval were calculated from the farm recording data. Serum triglyceride, non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB) concentrations were significantly increased after calving in summer compared to winter, indicating higher degree of NEB in cows during summer. PON1 activity was significantly decreased after calving in both summer and winter group. TAS concentration was significantly lower in summer than that in winter. A significantly higher number of services were needed for conception in summer compared to winter, and CC interval was significantly longer in summer than that in winter as well. Additionally, reproductive performance significantly correlated with the severity of NEB, suggesting that lipid mobilization and lower antioxidant status contributed to poor reproduction ability in dairy cows during hot months.
Asunto(s)
Antioxidantes/análisis , Bovinos/fisiología , Calor , Movilización Lipídica/fisiología , Reproducción/fisiología , Estaciones del Año , Animales , Industria Lechera , Ácidos Grasos no Esterificados/sangre , Femenino , Fertilidad , Lactancia , Embarazo , Factores de TiempoRESUMEN
Despite broad medical application, induction of artificial hypometabolism in vitro and its biochemical consequence have been rarely addressed. This study aimed to elucidate whether 3-iodothyronamine (T1AM) induces hypometabolism in an in vitro model with activation of AMP-activated protein kinase (AMPK) and whether it leads to a switch in primary fuel from carbohydrates to lipids as observed in in vivo models. Mouse C2C12 myotube and T1AM, a natural derivative of thyroid hormone, were used in this study. The oxygen consumption rate (OCR) decreased in a dose-dependent manner in response to 0-100 µM T1AM for up to 10 h. Upon 6-h of exposure to 75 µM T1AM, the OCR was reduced to 60 vs. ~ 95% for the control. The intracellular [AMP]/[ATP] was 1.35-fold higher in T1AM-treated cells. RT-PCR and immunoblotting analyses revealed that treated cells had upregulated p-AMPK/AMPK (1.8-fold), carnitine palmitoyl transferase 1 mRNA, and pyruvate dehydrogenase kinase, and downregulated acetyl CoA carboxylase (0.4-fold) and pyruvate dehydrogenase phosphatase. The treated cells had darker periodic acid-Schiff staining with 1.2-fold greater glycogen content than controls. Taken together, the hypometabolic response of myotubes to T1AM was dramatic and accompanied by increases in both the relative abundance of AMP and AMPK activation, and fuel choice favoring lipids over carbohydrates. These results are consistent with the general trends observed for rodent models and true hibernators.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Movilización Lipídica/fisiología , Fibras Musculares Esqueléticas/metabolismo , Consumo de Oxígeno/fisiología , Tironinas/metabolismo , Animales , Células Cultivadas , Ratones , MioblastosRESUMEN
Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liver-like oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulin-like peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance.
Asunto(s)
Adaptación Fisiológica/fisiología , Proteínas de Drosophila/metabolismo , Drosophila/fisiología , Ayuno/fisiología , Insulina/metabolismo , Movilización Lipídica/fisiología , Redes y Vías Metabólicas/fisiología , Somatomedinas/metabolismo , Animales , Secuencia de Bases , Proteínas de Drosophila/genética , Ectodermo/citología , Ectodermo/metabolismo , Cuerpo Adiposo/metabolismo , Microscopía Confocal , Datos de Secuencia Molecular , Análisis de Secuencia de ARN , Somatomedinas/genéticaRESUMEN
The incidence and severity of disease in cows is greatest during the transition period, when immune functions are impaired. Intense lipid mobilization is associated with both metabolic and infectious diseases in the transition cow. Significant increases in plasma nonesterified fatty acids contribute to oxidative stress and uncontrolled inflammatory responses. A dysfunctional inflammatory response is the common link between metabolic and infectious diseases around the time of calving. Intervention strategies that can reduce lipid mobilization may improve inflammatory responses and reduce the economic losses associated with health disorders during the transition period.
Asunto(s)
Enfermedades de los Bovinos/metabolismo , Inflamación/veterinaria , Lactancia/fisiología , Movilización Lipídica/fisiología , Trastornos Puerperales/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/fisiopatología , Ácidos Grasos no Esterificados/sangre , Femenino , Inflamación/inmunología , Inflamación/metabolismo , Lactancia/metabolismo , Estrés Oxidativo/fisiología , Embarazo , Trastornos Puerperales/inmunología , Trastornos Puerperales/metabolismo , Trastornos Puerperales/fisiopatología , Estrés Fisiológico/fisiologíaRESUMEN
Exercise in water compared to land-based exercise (LE) results in a higher release of natriuretic peptides, which are involved in the regulation of exercise-induced adipose tissue lipolysis. The present study was performed to compare the release of atrial natriuretic peptide (ANP) and free fatty acids (FFA) during prolonged aerobic water-based exercise (WE) with the release after an identical LE. 14 untrained overweight subjects performed 2 steady state workload tests on the same ergometer in water and on land. Before and after exercise, venous blood samples were collected for measuring ANP, FFA, epinephrine, norepinephrine, insulin and glucose. The respiratory exchange ratio (RER) was determined for fat oxidation.The exercises resulted in a significant increase in ANP in LE (61%) and in WE (177%), and FFA increased about 3-fold in LE and WE with no significant difference between the groups. Epinephrine increased, while insulin decreased similarly in both groups. The RER values decreased during the exercises, but there was no significant difference between LE and WE. In conclusion, the higher ANP concentrations in WE had no additional effect on lipid mobilization, FFA release and fat oxidation. Moderate-intensity exercises in water offer no benefit regarding adipose tissue lipolysis in comparison to LE.
Asunto(s)
Tejido Adiposo/metabolismo , Factor Natriurético Atrial/metabolismo , Ejercicio Físico/fisiología , Sobrepeso/metabolismo , Adulto , Estudios Cruzados , Epinefrina/metabolismo , Prueba de Esfuerzo/métodos , Ácidos Grasos no Esterificados/metabolismo , Femenino , Glucosa/metabolismo , Humanos , Insulina/metabolismo , Movilización Lipídica/fisiología , Masculino , Persona de Mediana Edad , Norepinefrina/metabolismo , Oxidación-Reducción , AguaRESUMEN
Lipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional cofactor transducin beta-like-related 1(TBLR1) blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and, when placed on a high-fat-diet, show aggravated adiposity, glucose intolerance, and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFAs). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes might thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders.
Asunto(s)
Tejido Adiposo Blanco/metabolismo , Movilización Lipídica/fisiología , Receptores Citoplasmáticos y Nucleares/metabolismo , Células 3T3-L1 , Animales , AMP Cíclico/metabolismo , Dieta Alta en Grasa , Ácidos Grasos no Esterificados/sangre , Humanos , Resistencia a la Insulina , Lipólisis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Obesidad/metabolismo , Obesidad/patología , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/genética , Transducción de SeñalRESUMEN
The transition period of dairy cattle is characterized by dramatic changes in metabolism and host defense mechanisms that are associated with increased disease. Intense lipid mobilization from tissue stores is an important metabolic adaptation during the transition period that results in significant release of non-esterified fatty acids (NEFA) into the blood stream. Whereas these fatty acids are important sources of energy during times of increased metabolic demands, elevated concentrations of NEFA are known to disrupt several immune and inflammatory functions. This review will discuss the implications of lipid mobilization on inflammatory responses with special emphasis on leukocytes and endothelial cell functions during the transition period of dairy cows.
Asunto(s)
Inflamación/inmunología , Movilización Lipídica/fisiología , Animales , Bovinos , Industria Lechera , Células Endoteliales/inmunología , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Femenino , Leucocitos/inmunologíaRESUMEN
AIM: The aim of this study was to evaluate serum and gingival crevicular fluid (GCF) pro-inflammatory cytokine levels in association between periodontal disease and hyperlipidaemia. MATERIAL AND METHODS: One hundred and twenty-three subjects with hyperlipidaemia and 68 systemically healthy controls (C) were included in the study. Hyperlipidaemic groups were divided into two groups as suggested diet (HD) and prescribed statin (HS). Both groups were divided into three subgroups as healthy (h), gingivitis (g) and periodontitis (p). The clinical periodontal parameters, fasting venous blood and GCF samples were obtained, and serum tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß (IL-1ß) and IL-6 levels were evaluated. RESULTS: The ratio of total cholesterol to high-density lipoprotein (TC/HDL) was associated with gingival index and percentage of bleeding on probing (BOP%) in both hyperlipidaemic groups. In HS group, GCF and serum IL-6 were positively correlated with BOP% and TC/HDL. GCF TNF-α was positively associated with probing pocket depth and clinical attachment level, whereas serum TNF-α was associated with BOP% in the HD group. Serum and GCF TNF-α and IL-1ß were significantly associated with TC/HDL in the HD group. CONCLUSIONS: Serum pro-inflammatory cytokines may play an important role in the association between periodontal disease and hyperlipidaemia.