Increased Fatty Acid Desaturation and Enhanced Expression of Stearoyl Coenzyme A Desaturase Protects Pancreatic β-Cells from Lipoapoptosis

Busch, Anna K.; Gurisik, Ebru; Cordery, Damien V.; Sudlow, Michelle; Denyer, Gareth; Laybutt, D. Ross; Hughes, William E.; Biden, Trevor J.

doi:10.2337/diabetes.54.10.2917

Cited by 165 publications

(169 citation statements)

References 38 publications

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“…In ob/ob mice, Scd1 deficiency caused the appearance of an abnormal class of pancreatic islets with reduced insulin content, suggesting that β-cell failure is responsible for the diabetic phenotype [50 •• ]. Consistent with this model, an in-vitro study using the MIN6 β-cell line found that increased expression of Scd1 protects against lipoapoptosis due to the enhanced desaturation of cytotoxic palmitate [76].…”

Section: Scd1 Deficiency: Friend or Foe For Diabetesmentioning

confidence: 52%

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

Flowers

Ntambi

2008

Current Opinion in Lipidology

382

312

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Purpose of review-Stearoyl-coenzyme A desaturase 1 is a δ-9 fatty acid desaturase that catalyzes the synthesis of monounsaturated fatty acids and has emerged as a key regulator of metabolism. This review evaluates the latest advances in our understanding of the pivotal role of stearoyl-coenzyme A desaturase 1 in health and disease.Recent findings-scd1-deficient mice have reduced lipid synthesis and enhanced lipid oxidation, thermogenesis and insulin sensitivity in various tissues including liver, muscle and adipose tissue due to transcriptional and posttranscriptional effects. These metabolic changes protect scd1-deficient mice from a variety of dietary, pharmacological and genetic conditions that promote obesity, insulin resistance and hepatic steatosis. Stearoylcoenzyme A desaturase 1 is required to guard against dietary unsaturated fat deficiency, leptin deficiency-induced diabetes, and palmitate-induced lipotoxic insults in muscle and pancreatic β-cells. Paradoxical observations of increased muscle stearoyl-coenzyme A desaturase 1 during obesity, starvation and exercise raise questions as to the role of stearoyl-coenzyme A desaturase 1 in this tissue. Mice with a liverspecific loss of stearoyl-coenzyme A desaturase 1, and inhibition of stearoyl-coenzyme A desaturase 1 via antisense or RNA interference, recapitulate only a subset of the phenotypes observed in global Scd1 deficiency, indicating the involvement of multiple tissues.Summary-Recent studies in humans and animal models have highlighted that modulation of stearoyl-coenzyme A desaturase 1 activity by dietary intervention or genetic manipulation strongly influences several facets of energy metabolism to affect susceptibility to obesity, insulin resistance, diabetes and hyperlipidemia.

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Section: Scd1 Deficiency: Friend or Foe For Diabetesmentioning

confidence: 52%

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

Flowers

Ntambi

2008

Current Opinion in Lipidology

382

312

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“…two diets, as it has been shown that different types of SFA have different functions and different metabolic effects (27) ; and (ii) the protective effect of unsaturated fats against the deleterious effect of SFA, as suggested by the results of some in vitro studies (28,29) . The prevalence of impaired fasting glucose was lowest in the starch group (21?4 %); this value was quite comparable to those in the other clusters, but fairly smaller than the highest value (38?1 %) in the animal products group.…”

Section: Discussionmentioning

confidence: 99%

Dietary patterns and metabolic syndrome factors in a non-diabetic Italian population

Leite

Nicolosi

2009

Public Health Nutr.

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Objective: To examine the relationship between dietary patterns and metabolic syndrome. Design: Population-based cross-sectional study. The K-means clustering method was used to identify dietary patterns and logistic regression models were used to compare the adjusted prevalence rates of metabolic syndrome factors, stratifying by obesity status. Setting: The 1992-3 Italian Bollate Eye Study, a population-based survey carried out in the town of Bollate (Milan), Italy. Subjects: A total of 1052 non-diabetic Italian subjects, 527 men and 525 women, aged 42-74 years. Results: Five dietary clusters were identified: common, animal products, starch, vegetal/fat and vitamin/fibre. After adjusting for potential confounders, the starch group showed the highest prevalence of metabolic syndrome (36 %) followed by the animal products group (30 %); the vitamin/fibre (20 %) and vegetal/fat groups (19 %) showed the lowest prevalence. The starch group had more dyslipidaemia (higher TAG and lower HDL cholesterol levels) and the animal products group had a higher prevalence of impaired fasting glucose. The vitamin/fibre group had the lowest prevalence of abdominal obesity. The beneficial effect of the vegetal/ fat and vitamin/fibre dietary patterns seemed stronger among the obese. Conclusions: Our results confirm the deleterious effect of a very-low-fat, highcarbohydrate diet and also of high intakes of animal products. The consumption of a diet high in vegetal fats or rich in fruits and vegetables is associated with a healthier metabolic profile. Reducing obesity is essential to prevent metabolic syndrome, but even among the obese dietary habits are important for preserving healthy lipid and glycaemic profiles. Keywords Metabolic syndromeDietary patterns Obesity Dyslipidaemia Cluster analysis Metabolic syndrome indicates a group of markersabdominal obesity, atherogenic dyslipidaemia, increased blood pressure and high plasma glucose levels -whose presence points to a very high risk of developing diabetes or CVD. These outcomes can be effectively prevented by early syndrome management, particularly including lifestyle modifications (1) .It is widely recognised that a healthy balanced diet is one of the principal elements in the prevention of diabetes and CVD, but it is still unclear which dietary pattern is the most beneficial for the successful management of metabolic syndrome and its complications, especially regarding the proportion and type of carbohydrates and fat (2)(3)(4) . Furthermore, the possible influence of conditions such as overweight and obesity on the relationship between diet and the metabolic syndrome needs to be evaluated (5) .We used the database of the Italian Bollate Eye Study (6)(7)(8) to examine the relationships between dietary patterns and metabolic syndrome factors in an adult population. MethodsWe used data from the 1992-3 Italian Bollate Eye Study, which was designed to investigate the prevalence and risk factors of major eye diseases in a population consisting of a random sample of all individu...

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“…Sixteen hours after attachment, cells were treated with 0.4 mmol/l palmitate coupled to 0.9% (wt/vol.) BSA and 0.74 MBq/ml [U-14 C] palmitate (1.76 TBq/mol) for 24 h. To measure [ 14 C] palmitate incorporation, lipids were extracted from the cells and analysed by TLC as described previously [9,20]. For secretion studies, cells were further incubated in palmitatefree medium for 24 h. Lipids were extracted from the cell culture medium and analysed by TLC.…”

Section: Indirect Calorimetry Oxygen Consumption (mentioning

confidence: 99%

Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice

et al. 2011

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Aims/hypothesis We examined the time-dependent effects of deletion of the gene encoding protein kinase C epsilon (Prkce) on glucose homeostasis, insulin secretion and hepatic lipid metabolism in fat-fed mice. Methods Prkce −/− and wild-type (WT) mice were fed a high-fat diet for 1 to 16 weeks and subjected to i.p. glucose tolerance tests (ipGTT) and indirect calorimetry. We also investigated gene expression and protein levels by RT-PCR, quantitative protein profiling (isobaric tag for relative and absolute quantification; iTRAQ) and immunoblotting. Lipid levels, mitochondrial oxidative capacity and lipid metabolism were assessed in liver and primary hepatocytes.Results While fat-fed WT mice became glucose intolerant after 1 week, Prkce −/− mice exhibited normal glucose and insulin levels. iTRAQ suggested differences in lipid metabolism and oxidative phosphorylation between fat-fed WT and Prkce −/− animals. Liver triacylglycerols were increased in fat-fed Prkce −/− mice, resulting from altered lipid partitioning which promoted esterification of fatty acids in hepatocytes. In WT mice, fat feeding elevated oxygen consumption in vivo and in isolated liver mitochondria, but these increases were not seen in Prkce −/− mice. Prkce −/− hepatocytes also exhibited reduced production of reactive oxygen species (ROS) in the presence of palmitate. After 16 weeks of fat feeding, however, the improved glucose tolerance in fat-fed Prkce −/− mice was instead associated with increased insulin secretion during ipGTT, as we have previously reported. Conclusions/interpretation Prkce deletion ameliorates dietinduced glucose intolerance via two temporally distinct phenotypes. Protection against insulin resistance is associated with changes in hepatic lipid partitioning, which may reduce the acute inhibitory effects of fatty acid catabolism, such as ROS generation. In the longer term, enhancement of glucose-stimulated insulin secretion prevails.

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Increased Fatty Acid Desaturation and Enhanced Expression of Stearoyl Coenzyme A Desaturase Protects Pancreatic β-Cells from Lipoapoptosis

Cited by 165 publications

References 38 publications

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism

Dietary patterns and metabolic syndrome factors in a non-diabetic Italian population

Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice

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