- SRC-3/AIB-1 Enhances Hepatic NFATC1 Transcription and Mediates Inflammation in a Tissue-Specific Manner in Morbid Obesity. [Journal Article]
- EMEndocr Metab Immune Disord Drug Targets 2019 Jul 15
- CONCLUSIONS: Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead in numerous cardiometabolic diseases. Further on, present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.
- Investigation of galectin-3, lipocalin 2, retinol binding protein (RBP), small dense low-density lipoprotein (sdLDL) in patients with hirsutism. [Journal Article]
- PDPostepy Dermatol Alergol 2019; 36(2):177-183
- CONCLUSIONS: No significant correlation was found between the adipokines that play a role in the aetiology of numerous diseases and some mediators of the lipid metabolism and hirsutism.
- From syndrome X to cardiometabolic risk: clinical and public health implications. [Journal Article]
- PNProc Nutr Soc 2019 Jul 18; :1-7
- Although the first description of a syndrome defined by the co-existence of atherogenic and diabetogenic metabolic abnormalities is debated in the literature, it was Gerald Reaven who proposed, in hi…
Although the first description of a syndrome defined by the co-existence of atherogenic and diabetogenic metabolic abnormalities is debated in the literature, it was Gerald Reaven who proposed, in his landmark 1988 Banting award lecture, that a significant proportion of individuals (with diabetes or not) were characterised by insulin resistance causing prejudice to cardiovascular health. However, Reaven was influenced by seminal observations made more than 50 years earlier by Himsworth who proposed that there were two forms of diabetes (insulin resistant v. insulin sensitive). Reaven went further in proposing the theory that insulin resistance was the most prevalent cause of CVD associated with metabolic abnormalities that he named syndrome X. Because there was a syndrome X documented in cardiology, the term evolved to insulin resistance syndrome. As Reaven could also find insulin-resistant individuals in non-obese subjects, he did not include obesity as a feature of syndrome X. Imaging studies then revealed that excess adipose tissue in the abdominal cavity, a condition described as visceral obesity, was the form of overweight/obesity associated with insulin resistance and its related abnormalities. As obesity risk assessment and management remain largely based on body weight (BMI) and weight loss, it is proposed that our clinical approaches and public health messages should be revisited. First, patients should be educated about the importance of monitoring their waistline as a crude index of abdominal adiposity. Secondly, public health approaches focussing on 'lifestyle vital signs' including achieving healthy waistlines rather than healthy body weights should be developed.
- Association of Plasma Procalcitonin with Various Components of Metabolic Syndrome and Insulin Resistance in Urban Indian Population: A Novel Biomarker. [Journal Article]
- JAJ Assoc Physicians India 2018; 66(12):35-38
- CONCLUSIONS: Raised plasma procalcitonin levels in the normal range are associated with insulin resistance and components of the metabolic syndrome (abdominal obesity, hypertriglyceridemia, high VLDL, low HDL and hyperglycemia), suggesting its role as a promising biomarker.
- The treatment with pasireotide in Cushing's disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center. [Journal Article]
- JEJ Endocrinol Invest 2019 Jul 16
- CONCLUSIONS: The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.
- Oil Red-O Positive lipid blobs on peripheral blood film examination in a muscular infant with the diagnosis of Berardinelli-Seip syndrome. [Case Reports]
- OMOxf Med Case Reports 2019; 2019(7):omz062
- Lipodystrophy syndromes can be acquired or hereditary in nature and are characterized by abnormal fat distribution including the inability of the body to develop and sustain healthy adipose tissue. T…
Lipodystrophy syndromes can be acquired or hereditary in nature and are characterized by abnormal fat distribution including the inability of the body to develop and sustain healthy adipose tissue. They may be generalized or partial in nature. The congenital generalized form is termed as Berardinelli-Seip syndrome and may occur due to mutations in the AGPAT2 or BSCL2 genes. In this case report, we present an infant diagnosed with type-1 Berardinelli-Seip syndrome due to pathogenic variation in the AGPAT2 gene. Though this type of lipodystrophy is less severe than the type-2 form, the case highlights the early presentation of the condition in infancy with increased frequency of stools and hypertriglyceridemia. In addition, we want to highlight that identification of characteristic physical appearances and recognition of abnormal findings during basic investigations is important, which can guide a clinician in making a correct diagnosis.
- Ethnic distinctions in the pathophysiology of type 2 diabetes: a focus on black African-Caribbean populations. [Journal Article]
- PNProc Nutr Soc 2019 Jul 16; :1-10
- Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechani…
Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.
- Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment. [Journal Article]
- EOExpert Opin Drug Saf 2019 Jul 19; :1-12
- Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases.…
Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.
- Luteolin reduces adipose tissue macrophage inflammation and insulin resistance in postmenopausal obese mice. [Journal Article]
- JNJ Nutr Biochem 2019 Jun 20; 71:72-81
- Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of lu…
Previously, we showed that loss of ovarian function in mice fed high-fat diet exacerbated insulin resistance and adipose tissue inflammation. In the current study, we tested whether consumption of luteolin, an anti-inflammatory flavonoid, could mitigate adipose tissue inflammation and insulin resistance in obese ovariectomized mice. Nine-week-old ovariectomized C57BL/6 mice were fed a low-fat diet, high-fat diet (HFD) or HFD supplemented with 0.005% luteolin (HFD+L) for 16 weeks. Results showed no difference in body weight or fat mass between mice fed HFD+L and those fed HFD. However, luteolin supplementation resulted in lower CD11c+ macrophages in gonadal adipose tissue, as well as a trend toward lower macrophage infiltration. Luteolin supplementation also significantly lowered mRNA expression of inflammatory and M1 markers MCP-1, CD11c, TNF-α and IL-6, while maintaining expression of M2 marker MGL1. Consistent with this, the in vitro luteolin treatment, with or without the presence of estrogen, inhibited lipopolysaccharide-induced polarization of RAW 264.7 cells toward M1 phenotype. We further found that luteolin supplementation protected mice from insulin resistance induced by HFD consumption; this improved insulin resistance was correlated with reductions in CD11c+ adipose tissue macrophages. Taken together, these findings indicate that dietary luteolin supplementation attenuates adipose tissue inflammation and insulin resistance found in mice with loss of ovarian function coupled with an HFD intake, and this effect may be partly mediated through suppressing M1-like polarization of macrophages in adipose tissue. These results have clinical implication in implementing dietary intervention for prevention of metabolic syndrome associated with postmenopause and obesity.
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- Secreted frizzled-related protein 4 and its implication in obesity and type-2 diabetes. [Review]
- ILIUBMB Life 2019 Jul 13
- Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These …
Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to β-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic β-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity-induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-β (IL1-β). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D.