•Berardinelli-Seip lipodystrophy is known as congenital generalized lipodystrophy, CGL.•CGL is rare and patients suffer with increased appetite and shortened life expectancy.•Patients present ...dyslipidemia, hypoleptinemia, ectopic fat deposition and lipotoxicity.•We found major differences in plasma lipidomic profile compared to healthy volunteers.•A fat-containing breakfast did not change lipidomic profile after 12 h fasting.
The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal.
Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry.
Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants.
The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.
Obesity and depression, disorders associated with inflammation, have high incidences in women. Understanding the derangements present in the initial phase of obesity may point to factors that could ...help avoiding disease aggravation. The present study aimed at investigating the effects of a 6-months interdisciplinary therapy for weight loss in women with grade I obesity. Before and after the therapy, 37 middle-aged women donated blood and responded to questionnaires for depression and anxiety symptoms. Inflammatory parameters were evaluated in serum and a preliminary screening of the plasma proteome was performed. The therapy decreased anthropometric, psychological scores, and serum levels of inflammatory parameters. Depression and anxiety scores correlated positively with some inflammatory parameters. The proteomic analysis showed changes in proteins related to cholesterol metabolism and inflammatory response. Interdisciplinary therapy improves anthropometric and inflammatory statuses and ameliorating psychological symptoms. The decrease of MCP-1 levels after interdisciplinary therapy has not been reported so far, at the best of our knowledge. The present demonstration of positive associations of inflammatory markers and psychological scores indicate that these mediators may be useful to monitor psychological status in obesity. The present proteome data, although preliminary, pointed to plasma alterations indicative of improvement of inflammation after interdisciplinary therapy.
Exacerbated expansion of adipose tissue seen in diet-induced obesity leads to endocrine dysfunction and disturbance in adipokine secretion, with such abnormal profile positively associated with type ...2 diabetes and other mild chronic inflammatory conditions.
extract (GbE), a mixture of polyphenols with antioxidant properties, has been recently investigated in a variety of experimental models of endocrine dysfunction, with several potentially beneficial effects identified, including improvement in insulin sensitivity in obese rats, and reduction of weight gain in ovariectomy-induced obesity and diet-induced obesity. The aim of this study was to investigate in high fat diet-induced obese male rats the effects of GbE supplementation for 2 weeks on adipocyte volume and adipose tissue lipid accumulation. GbE supplementation was effective in reducing energy intake in obese rats compared to the saline-treated placebo group. Epididymal adipocyte volume was reduced in GbE-supplemented rats, as were epididymal 1-
C-acetate incorporation into fatty acids, perilipin (
) and fatty acid synthase (
) mRNA, and FAS protein levels. Adipocyte hypertrophy in obesity is associated with insulin resistance, and in the present study we observed a reduction in the adipocyte volume of GbE-supplemented obese rats to dimensions equivalent to adipocytes from non-obese rats. GbE supplementation significantly reduced acetate accumulation and tended to reduce
H-oleate incorporation, into epididymal adipose tissue, suggesting a potentially anti-obesogenic effect in longer term therapies. Further studies that investigate the effects of GbE supplementation in other experimental models are required to fully elucidate its suggested beneficial effects on mild chronic inflammatory conditions.
The effect of fish oil (FO) treatment on high‐fat (HF) diet‐induced obesity and metabolic syndrome was addressed by analyzing dysfunctions in cells of different adipose depots. For this purpose, mice ...were initially induced to obesity for 8 weeks following a treatment with FO containing high concentration of EPA compared to DHA (5:1), for additional 8 weeks (by gavage, 3 times per week). Despite the higher fat intake, the HF group showed lower food intake but higher body weight, glucose intolerance and insulin resistance, significant dyslipidemia and increased liver, subcutaneous (inguinal‐ING) and visceral (retroperitoneal‐RP) adipose depots mass, accompanied by adipocyte hypertrophy and decreased cellularity in both adipose tissue depots. FO treatment reversed all these effects, as well as it improved the metabolic activities of isolated adipocytes, such as glucose uptake and lipolysis in both depots, and de novo synthesis of fatty acids in ING adipocytes. HF diet also significantly increased both the pro and anti‐inflammatory cytokines expression by adipocytes, while HF + FO did not differ from control group. Collectively, these data show that the concomitant administration of FO with the HF diet is able to revert metabolic changes triggered by the diet‐induced obesity, as well as to promote beneficial alterations in adipose cell activities. The main mechanism underlying all systemic effects involves direct and differential effects on ING and RP adipocytes.
The manuscript show relevant effects of fish oil (FO) treatment reversing both the metabolic syndrome induced by high‐fat diet (HF) and the changes in subcutaneous (inguinal ‐ING) and visceral (retroperitoneal ‐RP) adipocytes, such as glucose uptake, lipolysis, and lipogenesis. The major findings of our study is that the FO treatment reverses the deleterious effects caused by the excessive intake of a HF diet, and the mechanism involves, at least in part, direct and differential effects on ING and RP adipocytes. Altogether, these effects prevented adipocyte hypertrophy caused by HF diet and reflected in decreased adiposity. Additionally, FO treatment decreased the gene and protein expression of inflammation‐related factors. Thus, the work provided important evidence concerning the effectiveness of a low‐cost agent (as the FO) to treat the metabolic and inflammatory disorders triggered by obesity, which causes thousands of deaths annually and burdens the public coffers.
The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, ...side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy.
extract (GbE) has been described as a promising new pharmacological approach to treat obesity. In order to better comprehend the mechanisms involved with this potential effect, the present study evaluated the effects of GbE treatment on diet-induced obese rats, focusing on the proteome and the oxidative stress defense system of visceral adipose tissue. After 14 days treatment, GbE significantly modulated 25 proteins. Retroperitoneal adipose tissue of treated animals exhibited higher amounts of proteins associated with adipogenesis (decorin), carbon metabolism and mitochondrial function (citrate synthase), and a concomitant reduction in adipocyte hypertrophy. In parallel, GbE down-regulated proteins involved in oxidative stress (peroxiredoxin) and the inflammatory response (complement C3, mast cell protease 1, and Ig gamma-2B chain C region). Moreover, also related to oxidative stress defense, GbE stimulated catalase activity, reduced malondialdehyde levels (lipid peroxidation indicator), and increased lactoylglutathione lyase levels. It was concluded that GbE acts as an antioxidant agent, and improved the proteome profile and oxidative stress response in the adipose tissue of diet-induced obese rats.
Previous studies have shown that
extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the ...hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator.
Menopause is associated with increased risk to develop obesity but the mechanisms involved are not fully understood. We have shown that
extract (GbE) improved diet-induced obesity. Since GbE might be ...effective in the treatment of obesity related to menopause, avoiding the side effects of hormone replacement therapy, we investigated the effect of GbE on hypothalamic systems controlling energy homeostasis. Wistar rats were either ovariectomized (OVX) or Sham-operated. After 2 months, either 500 mg.kg
of GbE or vehicle were administered daily by gavage for 14 days. A subset of animals received an intracerebroventricular (i.c.v.) injection of serotonin (300 μg) or vehicle and food intake was measured after 12 and 24 h. Another subset was submitted to
microdialysis and 5-HT levels of the medial hypothalamus were measured by high performance liquid chromatography, before and up to 2 h after the administration of 500 mg.kg
of GbE. Additional animals were used for quantification of 5-HT
, 5-HT
, 5-HT
, 5-HTT, and pro-opiomelanocortin hypothalamic protein levels by Western blotting. OVX increased food intake and body weight and adiposity while GbE attenuated these alterations. i.c.v. serotonin significantly reduced food intake in Sham, Sham + GbE, and OVX + GbE groups while it failed to do so in the OVX group. In the OVX rats, GbE stimulated 5-HT microdialysate levels while it reduced hypothalamic 5-HTT protein levels. The results indicate that GbE improved the ovariectomy-induced resistance to serotonin hypophagia, at least in part through stimulation of the hypothalamic serotonergic activity. Since body weight gain is one of the most important consequences of menopause, the stimulation of the serotonergic transmission by GbE may represent a potential alternative therapy for menopause-related obesity.
•Gut microbiota plays a pivotal role in energy homeostasis.•High saturated fat diets induce obesity and disturb gut microbiota.•Ginkgo biloba extract (GbE) oral supplementation positively modulates ...gut microbiota.•GbE reduces Bacteroidetes/Firmicutes colon ratio in high fat diet-induced obese rats.•GbE could potentially be used to manage metabolic disruptions induced by obesity.
Gut microbiota (GM) modulation has been considered a nutritional approach to manage obesity. Reduced Firmicutes/Bacteroidetes ratio (F/B) is associated with reduced energy harvesting capacity from the diet, ameliorates endotoxemia and inflammation, and restores gut hormone signaling related to hypothalamic control of energy homeostasis. As anti-obesogenic and anti-inflammatory properties have been attributed to Ginkgo biloba extract (GbE), the present study investigated whether GbE supplementation for two weeks modulates the GM composition of obese rats.
Fifty-six 2-month-old male Wistar rats were submitted to a lard-rich diet-induced obesity protocol for 60 days (high-fat diet, HFD). Following the obesity-inducing period, rats were gavaged daily with GbE at 500 mg/kg (HFD+G group), or saline (HFD group), for 14 days. A 3rd group (pair-fed group, PF) was performed by mimicking the HFD group (saline administration) but with its food intake matched to the HFD+G group. Rats were euthanized on the 14th supplementation day. Stool DNA was extracted and amplified with V3–V4 region primers of the 16S rRNA gene.
In comparison to both HFD and PF groups, GbE supplementation increased the number of Bacteroidetes colon community and concomitantly reduced the abundance of Firmicutes, reducing the F/B ratio. Hierarchical clustering showed that communities of the HFD+G group were less likely related to HFD and PF groups.
As GbE modulated the GM structure and diversity in GbE-supplemented obese rats, our results show that GbE possesses phytotherapeutic potential to modulate obesity by improving GM and lessening the consequences of obesity-related GM dysbiosis.
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Using rats we examined whether maternal intake of hydrogenated fat rich in trans fatty acids affects brain fatty acid profile, hypothalamic content of insulin receptor and insulin receptor ...substrate-1 proteins, and the hypophagic effect of centrally administered insulin in 3-mo-old male progeny.
Throughout pregnancy and lactation, Wistar rats ate isocaloric/normolipidic diets with soybean oil (control) or soybean oil-derived hydrogenated fat (trans diet) as a fat source. Upon weaning, the trans offspring continued on the trans diet (trans group) or were switched to a control diet (trans-control group).
Compared with control rats, trans rats had lower brain levels of eicosapentaenoic acid. Compared with trans rats, trans-control rats had increased levels of total polyunsaturated fatty acids and arachidonic acid and decreased levels of trans fatty acids, saturated fatty acids, and monounsaturated fatty acids. Insulin receptor and insulin receptor substrate-1 levels were significantly lower (44% and 38%, respectively) in trans than in control rats. In trans-control rats, insulin receptor was 26% lower (
P < 0.05), whereas insulin receptor substrate-1 was 50% lower, than in control rats. Insulin decreased 24-h feeding in control (27%) and trans (38%) rats but failed to do so in trans-control rats. The latter group had increased serum glucose levels.
The data suggest that the early (intrauterine/perinatal) exposure to hydrogenated fat rich in trans fatty acids programmed the hypothalamic feeding control mechanisms. As young adults, only trans-control animals showed loss of insulin-induced hypophagia, indicating that the mismatch between early and later nutritional environments was relevant. However, the trans group also showed signs of altered appetite signaling mechanisms, suggesting that the early adaptations may have deleterious consequences later in life.
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