Diseases of adipose tissue: genetic and acquired lipodystrophies

2005 ◽  
Vol 33 (5) ◽  
pp. 1073-1077 ◽  
Author(s):  
J. Capeau ◽  
J. Magré ◽  
O. Lascols ◽  
M. Caron ◽  
V. Béréziat ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Antiretroviral Drugs ◽  
Premature Aging ◽  
Peroxisome Proliferator ◽  
Loss Of Function ◽  
Lifestyle Modifications ◽  
Metabolic Alterations ◽  
Severe Insulin Resistance ◽  
The Metabolic Syndrome ◽  
Triacylglycerol Synthesis

Human lipodystrophies represent a group of diseases characterized by altered body fat amount and/or repartition and major metabolic alterations with insulin resistance leading to diabetic complications and increased cardiovascular and hepatic risk. Genetic forms of lipodystrophies are rare. Congenital generalized lipodystrophy or Berardinelli–Seip syndrome, autosomal recessive, is characterized by a complete early lipoatrophy and severe insulin resistance and results, in most cases, from mutations either in the seipin gene of unknown function or AGPAT2 encoding an enzyme involved in triacylglycerol synthesis. The Dunnigan syndrome [FPLD2 (familial partial lipodystrophy of the Dunnigan type)] is due to mutations in LMNA encoding the lamin A/C, belonging to the complex group of laminopathies that could comprise muscular and cardiac dystrophies, neuropathies and syndromes of premature aging. Some FPLDs are linked to loss-of-function mutations in the PPAR-γ gene (peroxisome-proliferator-activated receptor γ; FPLD3) with severe metabolic alterations but a less severe lipodystrophy compared with FPLD2. The metabolic syndrome, acquired, represents the most common form of lipodystrophy. HIV-infected patients often present lipodystrophies, mainly related to side effects of antiretroviral drugs together with insulin resistance and metabolic alterations. Such syndromes help to understand the mechanisms involved in insulin resistance resulting from altered fat repartition and could benefit from insulin-sensitizing effects of lifestyle modifications or of specific medications.

scholarly journals Electronic Cigarette Use and Metabolic Syndrome Development: A Critical Review

Toxics ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 105
Author(s):  
Ilona Górna ◽  
Marta Napierala ◽  
Ewa Florek
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Arterial Blood Pressure ◽  
Abdominal Obesity ◽  
Critical Review ◽  
Lifestyle Modifications ◽  
The Metabolic Syndrome ◽  
Arterial Blood ◽  
The Impact

The metabolic syndrome is a combination of several metabolic disorders, such as cardiovascular disease, atherosclerosis, and type 2 diabetes. Lifestyle modifications, including quitting smoking, are recommended to reduce the risk of metabolic syndrome and its associated complications. Not much research has been conducted in the field of e-cigarettes and the risk of metabolic syndrome. Furthermore, taking into account the influence of e-cigarettes vaping on the individual components of metabolic syndrome, i.e, abdominal obesity, insulin resistance, dyslipidemia and elevated arterial blood pressure, the results are also ambiguous. This article is a review and summary of existing reports on the impact of e-cigarettes on the development of metabolic syndrome as well as its individual components. A critical review for English language articles published until 30 June 2020 was made, using a PubMed (including MEDLINE), Cochrane, CINAHL Plus, and Web of Science data. The current research indicated that e-cigarettes use does not affect the development of insulin resistance, but could influence the level of glucose and pre-diabetic state development. The lipid of profile an increase in the TG level was reported, while the influence on the level of concentration of total cholesterol, LDL fraction, and HDL fraction differed. In most cases, e-cigarettes use increased the risk of developing abdominal obesity or higher arterial blood pressure. Further research is required to provide more evidence on this topic.

scholarly journals Peroxisome Proliferator–Activated Receptors and The Metabolic Syndrome

2009 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Energy Balance ◽  
Glucose Homeostasis ◽  
Gene Activation ◽  
Sugar Metabolism ◽  
Endocrine Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome

BACKGROUND: Obesity is a growing threat to global health by virtue of its association with insulin resistance, inflammation, hypertension, and dyslipidemia, collectively known as the metabolic syndrome (MetS). The nuclear receptors PPARα and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the PPARδ has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARs in the treatment of metabolic disease.CONTENT: We have learned much about PPARs, the metabolic fat sensors, and the molecular pathways they regulate. Through their distinct tissue distribution and specific target gene activation, the three PPARs together control diverse aspects of fatty acid metabolism, energy balance, insulin sensitivity glucose homeostasis, inflammation, hypertension and atherosclerosis. These studies have advanced our understanding of the etiology for the MetS. Mechanisms revealed by these studies highlight the importance of emerging concepts, such as the endocrine function of adipose tissue, tissue-tissue cross-talk and lipotoxicity, in the pathogenesis of type 2 diabetes mellitus and CVD.SUMMARY: The elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their intimate link. The three ‘lipidsensing’ (PPARα, PPARγ and PPARδ) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bonafide therapeutic targets.KEYWORDS: Peroxisome Proliferator, Activated Receptor, Metabolic Syndrome

scholarly journals Loss of adipocyte phospholipase gene PLAAT3 causes lipodystrophy and insulin resistance due to inactivated arachidonic acid-mediated PPAR𝛾 signaling

2021 ◽  
Author(s):  
Nika Schuermans ◽  
Salima El Chehadeh ◽  
Dimitri Hemelsoet ◽  
Elke Bogaert ◽  
Elke Debackere ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Arachidonic Acid ◽  
Drug Target ◽  
Loss Of Function ◽  
Membrane Phospholipids ◽  
Partial Lipodystrophy ◽  
Severe Insulin Resistance ◽  
Diet Induced Obesity ◽  
Candidate Drug ◽  
And Function

PLAAT3 is a phospholipid modifying enzyme predominantly expressed in white adipose tissue (WAT). It is a candidate drug target as Plaat3 deficiency in mice protects against picornavirus infection and diet-induced obesity. We identified four patients with homozygous loss-of-function mutations in PLAAT3, presenting with partial lipodystrophy, severe insulin resistance and dyslipidemia. PLAAT3-deficient WAT showed a failure to liberate arachidonic acid (AA) from membrane phospholipids resulting in an inactive gene network downstream of adipogenesis master regulator and anti-diabetic drug target PPARG. These findings establish PLAAT3 deficiency in humans as a novel type of partial lipodystrophy due to an AA- and PPARG-dependent defect in WAT differentiation and function.

scholarly journals Hexarelin, a Growth Hormone Secretagogue, Improves Lipid Metabolic Aberrations in Nonobese Insulin-Resistant Male MKR Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (10) ◽  
pp. 3174-3187 ◽  
Author(s):  
Rasha Mosa ◽  
Lili Huang ◽  
Yeda Wu ◽  
Chungyan Fung ◽  
Oshini Mallawakankanamalage ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Body Composition ◽  
Body Weight ◽  
Total Body Weight ◽  
Metabolic Effects ◽  
Growth Hormone Secretagogue ◽  
Severe Insulin Resistance ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Abstract Despite the occurrence of dyslipidemia and its contribution to the development of insulin resistance in obese subjects, a growing number of studies have described abnormal lipid profiles among leaner persons. For example, individuals with an abnormal paucity or distribution of fat (lipodystrophy) develop severe insulin resistance, dyslipidemia, and hepatic steatosis. Deranged adipocyte metabolism and differentiation contribute to ectopic fat deposition and consequent development of insulin resistance. Growth hormone (GH) therapy has been shown to correct body composition abnormalities in some lipodystrophy patients. However, little is known about the effects of GH-releasing peptides in this regard. Hexarelin, a GH secretagogue, has recently been shown to have beneficial effects on fat metabolism via the CD36 receptor. In this study, the effects of twice daily intraperitoneal injections of hexarelin (200 μg/kg body weight) were examined in nonobese insulin-resistant MKR mice and corresponding wild-type FVB mice for 12 days. Hexarelin treatment significantly improved glucose and insulin intolerance and decreased plasma and liver triglycerides in MKR mice. These beneficial metabolic effects could be due to the improved lipid metabolism and enhanced adipocyte differentiation of white adipose tissue with hexarelin treatment. Interestingly, although food intake of hexarelin-treated MKR mice was significantly increased, this did not change total body weight. Moreover, hexarelin treatment corrected the abnormal body composition of MKR mice, as demonstrated by a decrease in fat mass and an increase in lean mass. Our results suggest a possible application of hexarelin in treatment of lipid disorders associated with the metabolic syndrome.

scholarly journals Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Rinki Murphy ◽  
Richard W. Carroll ◽  
Jeremy D. Krebs
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Single Gene ◽  
Pancreatic Beta Cell ◽  
Caloric Intake ◽  
Primary Defect ◽  
Severe Insulin Resistance ◽  
Monogenic Disorders ◽  
The Metabolic Syndrome ◽  
Reduced Physical Activity

Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

scholarly journals Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents

2005 ◽  
Vol 35 (2) ◽  
pp. 373-380 ◽  
Author(s):  
S Sookoian ◽  
S I García ◽  
P I Porto ◽  
G Dieuzeide ◽  
C D González ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome ◽  
Arterial Blood ◽  
Blood Pressures

Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPARγ) (Pro12 Ala) and its coactivator PGC-1α (Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPARγ and PGC-1α genotypes. The 12 Ala PPARγ allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1α homozygotes had lower WHRs than other PGC-1α genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPARγ variant (odds ratio=4.0, 95% confidence interval 1.5–10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1α gene may be an independent genetic risk factor for young-onset hypertension.

scholarly journals Protein Oxidation in Metabolic Syndrome

2013 ◽  
Vol 36 (1) ◽  
pp. 1 ◽  
Author(s):  
Eugenia Hopps ◽  
Gregorio Caimi
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Protein Oxidation ◽  
Protein Carbonylation ◽  
Oxidation Products ◽  
Therapeutic Interventions ◽  
Lifestyle Modifications ◽  
The Metabolic Syndrome

Purpose: Oxidative stress plays a pivotal role in the pathogenesis of the metabolic syndrome and in the progression of its complications. Carbonylated proteins are a stable marker of severe oxidative stress because damage to the protein structure is irreversible and may cause an inhibition of their enzymatic activity or an increased susceptibility to proteolysis. There are few data regarding protein oxidation in metabolic syndrome, although elevated levels of carbonyl groups are often detected in subjects with obesity, diabetes mellitus, hypertension or dyslipidemia, well-known components of the metaboic syndrome. In particular, obesity, insulin resistance and diabetes mellitus are frequently associated with increased protein carbonylation. A relationship between insulin resistance, protein oxidative stress and inflammation has also been suggested as well as protein oxidation products are correlated with overexpression of resistin, TNF-α and IL-6. Conclusion: Therapeutic interventions based on lifestyle modifications and pharmacological agents in order to correct all the main risk factors influence oxidative stress and protein carbonylation.

Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia

2007 ◽  
Vol 293 (1) ◽  
pp. E172-E181 ◽  
Author(s):  
Angela C. Smith ◽  
Kerry L. Mullen ◽  
Kathryn A. Junkin ◽  
Jennifer Nickerson ◽  
Adrian Chabowski ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Transport ◽  
Citrate Synthase ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Triacylglycerol Synthesis ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 ± 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats ( P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-γ coactivator-1α, citrate synthase, and β-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle.

scholarly journals Lipodystrophy: metabolic insights from a rare disorder

2010 ◽  
Vol 207 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Isabel Huang-Doran ◽  
Alison Sleigh ◽  
Justin J Rochford ◽  
Stephen O'Rahilly ◽  
David B Savage
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Premature Mortality ◽  
Severe Insulin Resistance ◽  
The Metabolic Syndrome ◽  
Essential Components ◽  
Powerful Approach ◽  
Extreme Phenotypes ◽  
Adipose Tissue Development ◽  
Almost All

Obesity, insulin resistance and their attendant complications are among the leading causes of morbidity and premature mortality today, yet we are only in the early stages of understanding the molecular pathogenesis of these aberrant phenotypes. A powerful approach has been the study of rare patients with monogenic syndromes that manifest as extreme phenotypes. For example, there are striking similarities between the biochemical and clinical profiles of individuals with excess fat (obesity) and those with an abnormal paucity of fat (lipodystrophy), including severe insulin resistance, dyslipidaemia, hepatic steatosis and features of hyperandrogenism. Rare lipodystrophy patients therefore provide a tractable genetically defined model for the study of a prevalent human disease phenotype. Indeed, as we review herein, detailed study of these syndromes is beginning to yield valuable insights into the molecular genetics underlying different forms of lipodystrophy, the essential components of normal adipose tissue development and the mechanisms by which disturbances in adipose tissue function can lead to almost all the features of the metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document