133-OR: Dyrk1b Is a Nutrient-Sensing Protein That Triggers De Novo Lipogenesis by Activating mTORC2 Complex: Implication for the Treatment of Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 133-OR
Author(s):  
NEHA BHAT
Keyword(s):  
Type 2 Diabetes ◽  
De Novo ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Mtorc2 Complex

scholarly journals Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

2019 ◽  
Vol 7 (1) ◽  
pp. e000691 ◽  
Author(s):  
Waqas Qureshi ◽  
Ingrid D Santaren ◽  
Anthony J Hanley ◽  
Steven M Watkins ◽  
Carlos Lorenzo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Insulin Resistance Atherosclerosis Study

ObjectiveTo examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0),cis-palmitoleic acid (c16:1 n-7),cis-myristoleic acid (c14:1n5), stearic acid (18:0) andcis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity.Research design and methodsWe evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes.ResultsType 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR.ConclusionsWe observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

scholarly journals Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies

PLoS Medicine ◽  
2020 ◽  
Vol 17 (6) ◽  
pp. e1003102 ◽  
Author(s):  
Fumiaki Imamura ◽  
Amanda M. Fretts ◽  
Matti Marklund ◽  
Andres V. Ardisson Korat ◽  
Wei-Sin Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Cohort Studies ◽  
Prospective Cohort ◽  
De Novo ◽  
Pooled Analysis ◽  
De Novo Lipogenesis ◽  
Prospective Cohort Studies

scholarly journals Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats

2015 ◽  
Vol 40 (10) ◽  
pp. 1038-1047 ◽  
Author(s):  
Melissa A. Linden ◽  
Kristi T. Lopez ◽  
Justin A. Fletcher ◽  
E. Matthew Morris ◽  
Grace M. Meers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Liver Disease ◽  
Caloric Restriction ◽  
Fatty Liver Disease ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Oletf Rats

Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD is unclear. We assessed the effects of metformin, caloric restriction, and their combination on NAFLD in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (age 20 weeks; n = 6–8 per group) were fed ad libitum (AL), given metformin (300 mg·kg−1·day−1; Met), calorically restricted (70% of AL; CR), or calorically restricted and given metformin (CR+Met) for 12 weeks. Met lowered adiposity compared with AL but not to the same magnitude as CR or CR+Met (p < 0.05). Although only CR improved fasting insulin and glucose, the combination of CR+Met was needed to improve post-challenge glucose tolerance. All treatments lowered hepatic triglycerides, but further improvements were observed in the CR groups (p < 0.05, Met vs. CR or CR+Met) and a further reduction in serum alanine aminotransferases was observed in CR+Met rats. CR lowered markers of hepatic de novo lipogenesis (fatty acid synthase, acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase-1 (SCD-1)) and increased hepatic mitochondrial activity (palmitate oxidation and β-hydroxyacyl CoA dehydrogenase (β-HAD) activity). Changes were enhanced in the CR+Met group for ACC, SCD-1, β-HAD, and the mitophagy marker BNIP3. Met decreased total hepatic mTOR content and inhibited mTOR complex 1, which may have contributed to Met-induced reductions in de novo lipogenesis. These findings in the OLETF rat suggest that the combination of caloric restriction and metformin may provide a more optimal approach than either treatment alone in the management of type 2 diabetes and NAFLD.

scholarly journals A pilot study of the effects of pioglitazone and rosiglitazone on de novo lipogenesis in type 2 diabetes

2008 ◽  
Vol 49 (12) ◽  
pp. 2657-2663 ◽  
Author(s):  
Carine Beysen ◽  
Elizabeth J. Murphy ◽  
Hirisadarahally Nagaraja ◽  
Martin Decaris ◽  
Timothy Riiff ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pilot Study ◽  
De Novo ◽  
De Novo Lipogenesis

scholarly journals Circulating calcium levels and the risk of type 2 diabetes: a systematic review and meta-analysis

2019 ◽  
Vol 122 (04) ◽  
pp. 376-387 ◽  
Author(s):  
J. Zhu ◽  
P. Xun ◽  
J. C. Bae ◽  
J. H. Kim ◽  
D. J. Kim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Cohort Studies ◽  
Glucose Homeostasis ◽  
De Novo ◽  
Meta Analysis ◽  
Cross Sectional ◽  
Relative Risks ◽  
Ca Homeostasis

AbstractAbnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references withde novoresults from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n4) nor cross-sectional (n8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.

scholarly journals Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

Metabolomics ◽  
2020 ◽  
Vol 16 (1) ◽  
Author(s):  
David Balgoma ◽  
Sofia Zelleroth ◽  
Alfhild Grönbladh ◽  
Mathias Hallberg ◽  
Curt Pettersson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Metabolic Diseases ◽  
De Novo ◽  
High Resolution Mass Spectrometry ◽  
De Novo Lipogenesis ◽  
Anabolic Androgenic Steroids ◽  
Lipid Profiling ◽  
Testosterone Undecanoate ◽  
Androgenic Steroids

Abstract Introduction The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown. Objectives To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver. Methods We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry. Results Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid. Conclusion The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

scholarly journals Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

2010 ◽  
Vol 299 (3) ◽  
pp. R728-R739 ◽  
Author(s):  
Barbara E. Hasek ◽  
Laura K. Stewart ◽  
Tara M. Henagan ◽  
Anik Boudreau ◽  
Natalie R. Lenard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Uncoupling Protein ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Endocrine Function ◽  
Fischer 344 ◽  
Methionine Restriction ◽  
Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

Sign in / Sign up

Export Citation Format

Share Document