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Aims: Previous work has demonstrated that ketogenic diets promote white fat browning; however, the exact mechanisms underlying this phenomenom have yet to be elucidated. Recently, an in vitro study showed that supraphysiological concentrations of β-hydroxybutyrate (βHB) had a strong influence on the induction of adipocyte browning. On the other hand, concentrations in the physiological range, achieved through ketogenic diets and prolonged fasting produce values of 1-3 mM and 4-7 mM, respectively. Herein, we investigated the impact of physiological concentrations of βHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues., Main Methods: The effects of βHB on adipocyte browning were investigated in vitro, using primary cultures of isolated visceral and subcutaneous fat cells and cultured 3T3-L1 adipocytes, and in vivo., Key Findings: It was determined that βHB failed to induce changes in the oxidative capacity, citrate synthase activity or browning gene expression patterns in isolated adipocytes, and did not exert a permissive effect on β-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following βHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after βHB salt treatment. Rats administered βHB salts also presented reduced brown adipose tissue UCP1 protein expression., Significance: The mechanisms underlying ketogenic diet-induced browning of adipocytes are not known. The results from the present study indicate that physiological concentrations of βHB are not responsible for this phenomenon, despite the observed βHB-mediated downregulation of UCP1 expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: We investigated the effects of physical detraining on lipogenesis/lipolysis and cellularity (apoptosis/adipogenesis) in rat subcutaneous (inguinal; SC) and visceral (retroperitoneal; RP) white adipose depots., Main Methods: Three groups of male Wistar rats (6-wk old) were studied: (1) (T) trained for 12 weeks; (2) (D) trained for 8 weeks and detrained for 4 weeks; and (3) (S) age-matched sedentary. Training consisted of treadmill running sessions (1 h/day, 5 days/week, 50-60% maximal race capacity)., Key Findings: Physical detraining increased glucose oxidation, lipogenesis, and adipocyte size in the SC and RP depots. The number of apoptotic SC adipocytes was reduced by 53% in the T (p < 0.0001) and by 43% in the D (p < 0.001) as compared with S. RP adipocyte apoptosis in the T and D was 9.48% and 10.9% greater compared to the S, respectively (p < 0.05). In the SC stromal vascular fraction (SVF) of D rats, adiponectin, sterol regulatory element binding protein (SREBP)-1c, Peroxisome proliferator-activated receptor gamma (PPARγ), and Perilipin A mRNA expressions were more pronounced than S group, suggesting a more intense adipogenesis. This putative adipogenic effect was not observed in the RP depot. The physical detraining promoted rapid increase in the SC and RP depots however not through the same mechanisms., Significance: Physical detraining induced fat cell hypertrophy (increase of lipogenesis) in both SC and RP whereas hyperplasia (increase of adipogenesis and reduction of apoptosis) was found in SC only. These results indicate the mechanism associated with obesogenic effects of detraining varies with the fat depot., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis., Main Methods: At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays., Key Findings: The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group., Significance: Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function., (Copyright © 2017. Published by Elsevier Inc.)

Aim: Most studies developed to investigate the effects of glucocorticoids chronic treatment on white adipose tissue uses high doses of these hormones. This study analyzes some effects of a chronic, continuous and steady infusion of low-dose hydrocortisone and the relationship with lipid accumulation in white adipose depots in rats., Main Methods: Nineteen male Wistar rats were divided into control (CON) and cortisol (CORT) groups. Along six weeks CORT group received continuous infusion of 0.6mg/kg/day of hydrocortisone, while CON group received saline. After euthanasia, subcutaneous and visceral (retroperitoneal and mesenteric) fat pads were excised, weighted and analyzed for: lipogenic enzymes activity; molecular changes of 11-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme; enzymes involved in lipid uptake, incorporation, and metabolism and in fatty acids esterification. Besides, morphometric cell analysis was performed., Key Findings: CORT group showed increased triglycerides, changes in lipoprotein profile and 26,8% increment in central subcutaneous (SC) mass, while visceral fat pads masses remained unchanged. Adipocytes from SC, only, presented increased fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase activity, in addition to reduced AMP-activated protein kinase and 11βHSD1 enzymes content., Significance: Chronic low-dose hydrocortisone treatment consequences seem to be different from those commonly seen in long term hypercortisolism. While high doses promote lipid accumulation in visceral depots, a low dose showed an increase in central SC depot only. This appears to involve an increment in lipid storage and in de novo lipogenesis enzymes activity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Maternal hyperglycemia during pregnancy can lead to fetal changes, like macrosomia or obesity in adultlife. Experimentalmodels of diabetes have been studied to evaluate the consequences of offspring lipidmetabolism. This study aimed to investigate the metabolic changes in adipose tissue of offspring of streptozotocininduced diabetic mothers during neonatal period., Main Methods: Diabetes was induced in female rats by streptozotocin administration on 5th day of life. In adulthood, female rats were bred with control male rats. Male puppies were sacrificed on 12th week of life and epididymal (EP) and subcutaneous (SC) adipose fat pads were excised and weighted. Adipocytes were isolated and evaluated for basal and insulin-stimulated 2-deoxyglucose uptake, oxidation of glucose into CO2, and incorporationof glucose into lipids and lipolytic capacity., Key Findings: Bodyweight, EP fat padweight and diameter of adipocytes fromoffspring of diabeticmothers were increased in comparison to offspring of control mothers. EP adipocytes from offspring of diabetic mothers presented increased basal and insulin stimulated glucose uptake in comparison to control ones. Similar pattern was observed for glucose oxidation into CO2 and incorporation into lipids. However, significant difference in lipolytic capacity in vitrowas not observed. Protein content of GLUT4, insulin receptor and acetyl-CoA carboxylase was significantly increased in EP fat pad of offspring of diabetic mothers in relation to control group., Significance: Metabolic programming occurred in the adipose tissue of offspring of diabetic mothers, increasing its capacity to store lipids with no changes in lipolytic capacity.