Excessive caloric intake leading to obesity is associated with insulin resistance and dysfunction of islet β cells. High-fat feeding decreases desnutrin (also called ATGL/PNPLA2) levels in islets. ...Here we show that desnutrin ablation via RIP-Cre (βKO) or RIP-CreER results in hyperglycemia with impaired glucose-stimulated insulin secretion (GSIS). Due to decreased lipolysis, islets have higher TAG content but lower free FA levels. βKO islets exhibit impaired mitochondrial respiration and lower production of ATP required for GSIS, along with decreased expression of PPARδ target genes involved in mitochondrial oxidation. Furthermore, synthetic PPARδ, but not PPARα, agonist restores GSIS and expression of mitochondrial oxidative genes in βKO mice, revealing that desnutrin-catalyzed lipolysis generates PPARδ ligands. Finally, adenoviral expression of desnutrin in βKO islets restores all defects of βKO islet phenotype and function, including GSIS and mitochondrial defects, demonstrating the critical role of the desnutrin-PPARδ-mitochondrial oxidation axis in regulating islet β cell GSIS.
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•Desnutrin/ATGL ablation in islet β cells impairs insulin secretion (GSIS)•Desnutrin-catalyzed lipolysis governs TAG content and FA utilization in β cells•Desnutrin promotes mitochondrial function required for GSIS in β cells•PPARδ mediates the effects of desnutrin-catalyzed lipolysis on GSIS
This study aimed to assess the obesity effects on the proteomic profile of the periodontal ligament of rats submitted to obesity induction by a high-fat diet. Eight Holtzman rats were divided into ...control (n = 3) and obese (n = 5) groups. The maxillae were histologically processed for laser capture microdissection of the periodontal ligament of the first maxillary molars. Peptide mixtures were analyzed by LC-MS/MS. A total of 1379 proteins were identified in all groups. Among them, 335 (24.30%) were exclusively detected in the obese group, while 129 (9.35%) proteins were uniquely found in the control group. Out of the 110 (7.98%) differentially abundant proteins, 10 were more abundant and 100 had decreased abundance in the obese group. A gene ontology analysis showed some proteins related to obesity in the “extracellular exosome” term among differentially identified proteins in the gene ontology cellular component terms Prelp, Sec13, and Sod2. These three proteins were upregulated in the obese group (p < 0.05), as shown by proteomic and immunohistochemistry analyses. In summary, our study presents novel evidence that the proteomic profile of the periodontal ligament is altered in experimental obesity induction, providing a list of differentially abundant proteins associated with obesity, which indicates that the periodontal ligament is responsive to obesity.
We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested ...the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes.
For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 μM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes.
Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0.
Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lactation overnutrition is a programming agent of energy metabolism, and litter size reduction leads to the early development of obesity, which persists until adulthood. Liver metabolism is disrupted ...by obesity, and increased levels of circulating glucocorticoids are pointed as a possible mediator for the obesity development, since bilateral adrenalectomy (ADX) can reduce obesity in different models of obesity.
This study aimed to evaluate the effects of glucocorticoids on metabolic changes and liver lipogenesis and insulin pathway induced by lactation overnutrition. For this, on the postnatal day 3 (PND), 3 pups (small litter-SL) or 10 pups (normal litter-NL) were kept with each dam. On PND 60, male Wistar rats underwent bilateral adrenalectomy (ADX) or fictitious surgery (sham), and half of ADX animals received corticosterone (CORT- 25 mg/L) diluted in the drinking fluid. On PND 74, the animals were euthanized by decapitation for trunk blood collection, and liver dissection and storage.
SL rats presented increased corticosterone, free fatty acids, total and LDL-cholesterol plasma levels, without changes in triglycerides (TG) and HDL-cholesterol. The SL group also showed increased content of liver TG, and expression of fatty acid synthase (FASN), but decreased expression of PI3K
in the liver, compared to NL rats. In the SL group, the ADX decreased plasma levels of corticosterone, FFA, TG and HDL cholesterol, liver TG, and liver expression of FASN, and IRS2, compared to sham animals. In SL animals, CORT treatment increased plasma levels of TG and HDL cholesterol, liver TG, and expression of FASN, IRS1, and IRS2, compared with the ADX group. In summary, the ADX attenuated plasma and liver changes observed after lactation overnutrition, and CORT treatment could reverse most ADX-induced effects. Thus, increased circulating glucocorticoids are likely to play a pivotal role in liver and plasma impairments induced by lactation overnutrition in male rats.
Litter size reduction on the first days of life results in increased body weight and adiposity, with higher levels of circulating glucocorticoids. Obese rodents are more sensitive to the anabolic ...effects of glucocorticoids and less responsive to glucocorticoids feedback on hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to evaluate effects of the treatment with corticosterone on metabolic responses and HPA axis in adult male rats reared in small litters.
From postnatal day (PND) 60 to 88, adult male rats of normal (NL- 10 pups/dam) and small (SL- 3 pups/dam) litters received oral treatment with Corticosterone (CORT-15 mg/L) in the drinking water or no treatment, composing the four experimental groups (NL-water; NL-CORT; SL-water and SL-CORT), for the evaluation of energy homeostasis and HPA axis.
Male rats of SL-water group presented on PND88: glucose intolerance, higher adiposity, plasma triglycerides, free fatty acids, total and low-density lipoprotein (LDL) cholesterol and corticosterone. SL-water animals showed increased mRNA of corticotrophin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the pituitary, with decreased mRNA expression of PVN mineralocorticoid receptor. NL-CORT animals presented glucose intolerance, increased body weight, food intake, total and LDL cholesterol. Glucocorticoid treatment reduced corticosterone levels and adrenal cortex thickness in NL group, associated with increased mRNA of PVN CRH and pituitary POMC, without effects on SL animals.
Lactation overnutrition promotes hyperreactivity of HPA axis and reduces the responsiveness to glucocorticoids effects on energy balance and negative feedback of HPA axis in adult male rats.
Schematic diagram demonstrating that 1) corticosterone treatment in rats from normal litters (NL) caused metabolic changes (higher body weight, food intake, increased plasma levels of total and LDL cholesterol, and glucose intolerance) and adrenal gland atrophy, as observed by reduced thickness of adrenal cortex and corticosterone plasma levels, which induced higher expression of corticotrophin-releasing hormone (CRH) in the paraventricular nucleus of hypothalamus (PVN) and proopiomelanocortin (POMC) in the pituitary, due to the lack of negative feedback of glucocorticoids; 2) Male rats raised in small litters (SL) exhibited metabolic changes (glucose intolerance, adiposity, and dyslipidemia) and hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis (higher expression of CRH in the PVN, POMC in the pituitary and corticosterone plasma levels, associated with lower expression of MR in the PVN); 3) Obesity induced by litter size reduction impaired glucocorticoids effects on energy balance and HPA axis. Display omitted
•Litter size reduction induced obesity-related changes in adult male rats.•Early overnutrition induced hyperactivity of HPA axis and lower PVN MR expression.•Reduction of litter size impaired metabolic changes of exogenous glucocorticoids.•Neonatal overnutrition disrupted negative feedback of glucocorticoids on HPA axis.
This work evaluated the effects of neonatal overfeeding, induced by litter size reduction, on fertility and the noradrenaline-kisspeptin-gonadotrophin releasing hormone (GnRH) pathway in adult female ...rats. The litter size was adjusted to 3 pups with each mother in the small litters (SL) and 10 pups with each mother in the normal litters (NL). SL females exhibited metabolic changes associated with reproductive dysfunctions, shown by earlier vaginal opening and first estrus, later regular cyclicity onset, and lower and higher occurrences of estrus and diestrus phases, respectively, as well as reduced fertility, estradiol plasma levels, and mRNA expressions of tyrosine hydroxylase in the locus coeruleus, kisspeptin, and GnRH in the preoptic area in adult females in the afternoon of proestrus. These results suggest that neonatal overfeeding in female rats promotes reproductive dysfunctions in adulthood, such as lower estradiol plasma levels associated with impairments in fertility and noradrenaline-kisspeptin-GnRH pathway during positive feedback.
Graphical Abstract. Schematic diagram demonstrating that neonatal overfeeding induced by litter size reduction in female rats caused metabolic alterations: higher body weight, Lee index, adiposity, free fatty acids and corticosterone plasma levels, and glucose intolerance. These effects were associated with reproductive dysfunctions: earlier vaginal opening and first estrus, delayed estrous cycle regularization, estrous cycle dysregulation, as well as lower plasma estradiol concentrations related to reduced fertility and tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus (LC), and kisspeptin (Kiss) and gonadotropin releasing hormone (GnRH) mRNA expression in the preoptic area (POA) in adult females in the afternoon of proestrus. Display omitted
•Litter size reduction induced reproductive dysfunctions in female rats.•Obesity induced by neonatal overnutrition advanced puberty in females.•Reduction of litter size caused dysregulation of estrous cycle.•Neonatal overnutrition reduced estradiol plasma levels and fertility.
To compare the effects of Pilates with and without accessories on biochemical markers, pain intensity, functional disability and muscle strength in postmenopausal women with nonspecific chronic low ...back pain.
Twenty-two participants were randomized to a group of Pilates without (PG; n = 11) and with elastic resistance (PAG; n = 11) for 8 weeks, twice a week. We analyzed IGF-1, IGF-binding protein-3 (IGFBP-3), cortisol, creatine kinase, pain intensity, functional disability, abdominal and back strengths.
Both groups had lower pain intensity and functional disability and increased lumbar strength postinterventions. PAG exhibited an increase in IGF-1/IGFBP-3 ratio and reduction in creatine kinase compared with PG.
Both interventions were effective in the treatment of low back pain. However, PAG presented better responses than PG.
Brazilian Clinical Trials Registry: ReBEC (RBR-9jwcykc), www.ensaiosclinicos.gov.br/rg/RBR-9jwcykc.
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This study was designed to evaluate the beneficial effects of hyperglycemic metabolism after myocardial infarction as well as changes in sympathetic marker.
Male Wistar rats were ...divided into control (C), diabetic (D), myocardial infarction (MI) and diabetic myocardial infarction (DMI). Left coronary artery occlusion was performed after 15 or 30 days of diabetes (STZ) an accompanied by 2 or 15 days, respectively. The ventricular function, glycerol and norepinephrine levels were evaluated by echocardiography, biochemical kit and HPLC, respectively. The lipolysis was assessed by enzymes extracted from periepididymal adipose tissue. The area of infarction was 36% lower in DMI vs MI and the ejection (DMI: 82 ± 3 vs MI: 55 ± 3%) and shortening fraction (DMI: 48 ± 2 vs MI: 25 ± 2%) were preserved in DMI in comparison with MI. The glycerol was kept in 2 (2261 ± 180 mg/dl) and 15 (2756 ± 402 mg/dl) days after coronary occlusion in DMI, with 70% and 20% reduction in the weight of the adipose and adipocyte diameter as compared with D. The glycerol was decreased in MI after 2 (6245 ± 998) vs 15 (4355.45 ± 341mg/dl) days of MI vs C (7166 ± 1001mg/dl). Moreover, norepinephrine levels were decreased the MI group (5 ± 0.5 pg/ml) compared to the DMI (13 ± 1pg/ml). The results suggest an enhanced lipolysis in the MI group. Furthermore, diabetic animals had reduced infarcted area and improved ventricular function. These findings may be related to the increase in norepinephrine levels at the heart and the maintenance of lipolysis in this group, keeping thermogenesis in similar state as compared to normoglycemic animals.
There has been a great interest in developing zinc-based composites for biological applications. Mixing bioactive particles and obtaining a well-dispersed structure is not straight forward though. ...The present study reports a novel processing route in which zinc particles are mixed with hydroxyapatite and bioactive glass particles and consolidated at room temperature using high-pressure torsion. The composites display good dispersion of second phase particles, enhanced strength and an increased corrosion rate in the Hank’s balanced salt solution. The incorporation of these particles can be used to tailor the corrosion rate of zinc. It is shown that the surface layer of the corrosion product in the zinc-bioactive particle composites is richer in calcium and phosphorous than the pure zinc counterpart.
In this letter we study how deterministic features presented by a system can be used to perform direct transport in a {\it quasi}-symmetric potential and weak dissipative system. We show that the ...presence of nonhyperbolic regions around acceleration areas of the phase space plays an important role in the acceleration of particles giving rise to direct transport in the system. Such effect can be observed for a large interval of the weak asymmetric potential parameter allowing the possibility to obtain useful work from unbiased nonequilibrium fluctuation in real systems even in a presence of a {\it quasi}-symmetric potential.
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