Fat Metabolism In Adipose Tissue Research Articles

The New Role of AMP-Activated Protein Kinase in Regulating Fat Metabolism and Energy Expenditure in Adipose Tissue.

Obesity is characterized by excessive accumulation of fat in the body, which is triggered by a body energy intake larger than body energy consumption. Due to complications such as cardiovascular diseases, type 2 diabetes (T2DM), obstructive pneumonia and arthritis, as well as high mortality, morbidity and economic cost, obesity has become a major health problem. The global prevalence of obesity, and its comorbidities is escalating at alarming rates, demanding the development of additional classes of therapeutics to reduce the burden of disease further. As a central energy sensor, the AMP-activated protein kinase (AMPK) has recently been elucidated to play a paramount role in fat synthesis and catabolism, especially in regulating the energy expenditure of brown/beige adipose tissue and the browning of white adipose tissue (WAT). This review discussed the role of AMPK in fat metabolism in adipose tissue, emphasizing its role in the energy expenditure of brown/beige adipose tissue and browning of WAT. A deeper understanding of the role of AMPK in regulating fat metabolism and energy expenditure can provide new insights into obesity research and treatment.

Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism.

Purpose To explore the changes in FSP27 expression and fat metabolism in adipose tissue and their relationship after bariatric surgery in rats. Method Food intake, body weight, triglyceride content, fat distribution, and fat cell morphology were evaluated in rats grouped into control, sham, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) groups. Immunohistochemistry and western blotting were used to detect protein expression and real-time PCR was used to detect mRNA expression. Mouse 3T3-L1 preadipocytes were used to assess the effects of different energy levels and nutrient factors on FSP27 in adipocytes. Result Food intake, body weight, and triglyceride levels were reduced in RYGB and SG rats within 28 days after surgery, with a more pronounced effect in the RYGB group. Weight loss was mainly due to loss of fat mass rather than loss of lean mass, with the most pronounced decrease in trunk fat. FSP27 expression increased in lean rat adipocytes accompanied by increased lipid droplets (LDs). In SG and RYGB rats, the FSP27 protein concentration gradually increased in white adipose tissue (WAT) after operation. Hormone-sensitive lipase (HSL), p-HSL/HSL, Adipose Triglyceride Lipase (ATGL), and Comparative Gene Identification-58 (CGI-58) gradually decreased in SG and RYGB rats, but they were always higher than in control and sham animals. FSP27 was also decreased in 3T3-L1 adipocytes of animals with a high-energy diet. Conclusion FSP27 is associated with rat lipid metabolism and its expression varies with energy and nutrient supply. It can inhibit excessive hydrolysis and fat accumulation by regulating HSL and ATGL expression and by mediating LDs formation.

Differential effects of a combination of Hibiscus sabdariffa and Lippia citriodora polyphenols in overweight/obese subjects: A randomized controlled trial

Plant-polyphenols have shown the capacity to ameliorate obesity-induced metabolic disturbances, both in cell and animal models, where most therapeutic approaches have failed. On the basis of previous research, a dietary supplement containing 500 mg of a combination of polyphenolic extracts from Lippia citriodora L. and Hibiscus sabdariffa L. (LC-HS), in the context of an equilibrated isocaloric diet, was evaluated in a double blind, placebo-controlled and randomized trial in 56 obese/overweight subjects for two months. Compared to controls, the consumption of the LC-HS polyphenols showed significant improvements in body weight, abdominal circumference of overweight subjects (−6.79 ± 0.80 cm in overweight LC-HS group vs −1.85 ± 0.83 cm in controls, p < 0.001) and body fat % (−1.33 ± 0.15% in overweight LC-HS group vs −0.66 ± 0.17% in controls, p < 0.05). Heart rate and systolic blood pressure also presented significant improvements in overweight LC-HS participants. However, changes were more modest in obese subjects. Further, LC-HS extract significantly reduced lipid content and increased AMPK activity in a hypertrophied adipocyte cell model. Therefore, consumption of 500 mg/day of LC-HS extracts enriched in polyphenols for two months in the context of an isocaloric diet by overweight subjects decreased symptoms associated to obesity-related diseases. Modulation of fat metabolism in adipose tissue, probably mediated by AMPK activation, is proposed as a molecular target to be explored in future research.

Branched-chain amino acid ratios modulate lipid metabolism in adipose tissues of growing pigs

The effects and roles of branched-chain amino acid (BCAAs) ratios in lipid metabolism in adipose tissues of pigs are still unkown. We used pigs (Large White × Landrace, 35 ± 2 d) to investigate the effects of varying BCAA ratios (Leu: Ile: Val = 1:1:1, 1:0.75:0.75, 1:0.51:0.63, 1:0.25:0.25) on growth, carcass traits, and fat metabolism in adipose tissues. Results showed that as the ratio declined, the weight of total fat mass reduced while the adiponectin concentrations increased (P < .05), with the lowest/highest values observed in the 1:0.25:0.25 group, respectively. Moreover, varying BCAA ratios modulated the expression of genes related to adipose tissue function (P < .05). Concomitant with these changes, the 1:0.25:0.25 group increased/decreased the phosphorylation of AMPKα/mTOR, respectively (P < .05). The mRNA abundance of PGC-1α and IL-15 were also increased in diets with BCAA ratios from 1:0.75:0.75 to 1:0.25:0.25. Our data suggest that dietary BCAA ratios in the adequate range, i.e. 1:0.75:0.75–1:0.25:0.25, modulate adipose tissue function including fatty acid synthesis, transport, and oxidation, lipolysis, and adipokine secretion. These effects are partly mediated by AMPK-mTOR pathway and associated with mitochondrial biogenesis, the AMPK-PGC-1α axis, and IL-15 secreted by muscle tissues.

Transcriptome profile analysis of adipose tissues from fat and short-tailed sheep

Recent studies in domestic animals have used RNA-seq to explore the transcriptome of different tissues in a limited number of individuals. In the present study, de novo transcriptome sequencing was used to compare sheep adipose tissue transcriptome profiles between a fat-tailed breed (Kazak sheep; KS) and a short-tailed (Tibetan sheep; TS). The RNA-seq data from these two groups revealed that 646 genes were differentially expressed between the KS and TS groups, including 280 up-regulated and 366 down-regulated genes. We identified genes relevant to fat metabolism in adipose tissues, including two top genes with the largest fold change (NELL1 and FMO3). Pathway analysis revealed that the differentially expressed genes between the KS and TS breeds belong to fatty acid metabolism relevant pathways (e.g. fat digestion and absorption, glycine, serine, and threonine metabolism) and cell junction-related pathways (e.g. cell adhesion molecules) which contribute to fat deposition. This work highlighted potential genes and gene networks that affect fat deposition and meat quality in sheep.

Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

BackgroundOveractivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown.MethodsWe evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF) or a high-fat/fish oil (HF/FO) diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning.ResultsThe adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB1-/- mice.ConclusionsThese findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.

Prenatal Dexamethasone Programs Expression of Genes in Liver and Adipose Tissue and Increased Hepatic Lipid Accumulation But Not Obesity on a High-Fat Diet

The association between low birth weight and cardiovascular disease is amplified by the development of obesity. We explored the effects of postnatal high-fat (HF) feeding in dexamethasone (Dex)-programmed rats, in which prenatal glucocorticoid overexposure is associated with reduced birth weight and adult glucose intolerance. Male Wistar rats exposed to Dex or vehicle (Veh) during the last week of gestation were weaned onto HF or control diets for 6 months. Dex-exposed animals were of lower birth weight and showed catch-up growth by 7 wk. There were no differences in obesity or hyperinsulinaemia between Dex-HF and Veh-HF animals. However, Dex-HF animals had increased hepatic triglyceride content compared with Veh-HF animals. mRNA transcript profiles in adipose tissue revealed depot-specific changes in the expression of genes involved in fatty acid esterification and triglyceride synthesis and storage with prenatal Dex exposure. Thus, antenatal glucocorticoid overexposure in rats does not confer increased sensitivity to HF diet-induced obesity, but increases susceptibility to fatty liver. This may be due to depot-specific-programmed alterations in fat metabolism in adipose tissue.

Dysregulation of cannabinoid CB1 receptor expression in subcutaneous adipocytes of obese individuals

The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was ∼1.6‐fold (P<0.004) and 1.9‐fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non‐obese subjects in microarray and quantitative real‐time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (∼1.2 fold, P<0.05) and adipocytes (∼2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immuno‐fluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up‐regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.

Sympathetic and parasympathetic innervation of adipose tissue: metabolic implications

Adipose tissue is of fundamental importance for the integrative physiology of the body by serving metabolic and endocrine functions. The purpose of this review is to evaluate the functions of the autonomic innervation of adipose tissue. Different lines of evidence from studies on the sympathetic or parasympathetic innervation of adipose tissue have indicated that the autonomic nervous system modulates the fundamental properties of adipose tissue function and biology at the cellular and molecular level. This is reflected in the modulation of lipolysis/lipogenesis, local insulin sensitivity of glucose and fatty acid uptake, the expression levels of several adipokines in adipose tissue, and the modulation of fat cell number. In general, the function of the sympathetic nervous system can be described in terms of catabolism, whereas the function of the parasympathetic system can be described as anabolic. Innervation by autonomic nerves modulates glucose and fat metabolism in adipose tissue. It is very tempting to speculate on the effects of shifts in the balance between sympathetic and parasympathetic activity in adipose tissue in (patho)physiological conditions, such as lipodystrophy, type 2 diabetes mellitus, dyslipidemia and other insulin-resistant states.

Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice

Acc2-/- mutant mice, when fed a high-fat/high-carbohydrate (HF/HC) diet, were protected against diet-induced obesity and diabetes. To investigate the role of acetyl-CoA carboxylase 2 (ACC2) in the regulation of energy metabolism in adipose tissues, we studied fatty acid and glucose oxidation in primary cultures of adipocytes isolated from wild-type and Acc2-/- mutant mice fed either normal chow or a HF/HC diet. When fed normal chow, oxidation of [14C]palmitate in adipocytes of Acc2-/- mutant mice was approximately 80% higher than in adipocytes of WT mice, and it remained significantly higher in the presence of insulin. Interestingly, in addition to increased fatty acid oxidation, we also observed increased glucose oxidation in adipocytes of Acc2-/- mutant mice compared with that of WT mice. When fed a HF/HC diet for 4-5 months, adipocytes of Acc2-/- mutant mice maintained a 25% higher palmitate oxidation and a 2-fold higher glucose oxidation than WT mice. The mRNA level of glucose transporter 4 (GLUT4) decreased several fold in the adipose tissue of WT mice fed a HF/HC diet; however, in the adipose tissue of Acc2-/- mutant mice, it was 7-fold higher. Moreover, lipolysis activity was higher in adipocytes of Acc2-/- mutant mice compared with that in WT mice. These findings suggest that continuous fatty acid oxidation in the adipocytes of Acc2-/- mutant mice, combined with a higher level of glucose oxidation and a higher rate of lipolysis, are major factors leading to efficient maintenance of insulin sensitivity and leaner Acc2-/- mutant mice.

Glycerokinase in mammalian adipose tissue: stimulation by lipogenic substances

A connecting link between carbohydrate and fat metabolism in adipose tissue is theconcentration of alpha-glycerophosphate derived predominantly from the glycolysis ofglucose entering the fat cell. However, several investigators have reported the presence of a glycerol specific kinase in the epidiymal fat-pad of the rat and obob mouse. This enzyme's presence in other mammalian adipose tissue could contribute to the alpha-glycerophosphate pool and thus affect both carbohydrate and fat metabolism within the fat cell. Glycerokinase was demonstrated in isolated fat cells obtained from the subcutaneous, perirenal, epididymal, and dorsal intrascapular brown fat depots of the adultmale rat. It was found to be particularly sensitive to in vivo lipogenic stimuli in both the subcutaneous and the brown adipose tissue and concluded that insulin is involved in adipose glycerokinase stimulation. Therefore, the main function of glycerokinase in normal adipose tissue may be to augment the anabolic action of insulin. It isfurther suggested that deviation from the normal control of this lipogenic enzyme couldlead to a gradual accumulation of fat and eventual obesity.

Effect of ketone acids on glucose and fat metabolism in adipose tissue of the rat

Salts of the ketone acids, Na-beta-hydroxybutyric acid and Na acetoacetic acid, were injected intravenously into the normal rat and produced a sharp decrease in plasma FFA levels which persisted for one hour. No significant changes in levels of plasma glucose or insulin were observed. In vitro studies were performed using epididymal fat pads. Ketone acids were added to make a final concentration of 10 mmoles each. There was no significant effect on tissue glycogen, incorporation of labeled glucose into glycogen or production of C 14O 2, but there was an increase in the incorporation of C 14 into tissue lipids. The release of FFA and glycerol into medium was decreased. In another group of experiments, ketone acids were injected subcutaneously twice a day for three days. Adipose tissue from these animals reacted with increased glycogen, C 14-glycogen, C 14O 2 and C 14-lipids, and decreased release of FFA and glycerol. The impaired reaction of the adipose tissue of alloxan diabetic rats improved after treatment of these animals with ketone acids for three days. From these studies, we conclude that ketone acids have a minimal direct action on glucose metabolism in adipose tissue but a marked effect on fat metabolism with a definite decrease in FFA and glycerol release. Adipose tissue from ketone-acid-treated animals showed an insulin-like response suggesting that these acids in vivo do stimulate the insulin secreting cells of the pancreas. Both effect on fat tissue, direct and by employing insulin, result finally in a decrease of blood FFA levels; this may be of importance in prevention of development of severe ketoacidosis.