scholarly journals Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men

2019 ◽  
Vol 105 (5) ◽  
pp. 1501-1514 ◽  
Author(s):  
Katharina Kessler ◽  
Mathias J Gerl ◽  
Silke Hornemann ◽  
Markus Damm ◽  
Christian Klose ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Diurnal Variation ◽  
Saturated Fatty Acids ◽  
Insulin Response ◽  
Time Of Day ◽  
Diurnal Changes ◽  
High Fat ◽  
Shotgun Lipidomics ◽  
Meal Timing

Abstract Context Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. Objective We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. Design 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. Results 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. Conclusions This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity.

scholarly journals Macadamia Oil Supplementation Attenuates Inflammation and Adipocyte Hypertrophy in Obese Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Edson A. Lima ◽  
Loreana S. Silveira ◽  
Laureane N. Masi ◽  
Amanda R. Crisma ◽  
Mariana R. Davanso ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Lipid Profile ◽  
High Fat Diet ◽  
Control Diet ◽  
Saturated Fatty Acids ◽  
Peritoneal Macrophages ◽  
High Fat ◽  
Obesity In Mice ◽  
Adipocyte Hypertrophy

Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2 g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.

scholarly journals Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism

2013 ◽  
Vol 38 (5) ◽  
pp. 512-519 ◽  
Author(s):  
Andrea S. Cornford ◽  
Alexander Hinko ◽  
Rachael K. Nelson ◽  
Ariel L. Barkan ◽  
Jeffrey F. Horowitz
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Lipid Accumulation ◽  
Rapid Development ◽  
Insulin Response ◽  
Whole Body ◽  
Muscle Lipid ◽  
Wet Weight

Prolonged overeating and the resultant weight gain are clearly linked with the development of insulin resistance and other cardiometabolic abnormalities, but adaptations that occur after relatively short periods of overeating are not completely understood. The purpose of this study was to characterize metabolic adaptations that may accompany the development of insulin resistance after 2 weeks of overeating. Healthy, nonobese subjects (n = 9) were admitted to the hospital for 2 weeks, during which time they ate ∼4000 kcals·day−1 (70 kcal·kg−1 fat free mass·day−1). Insulin sensitivity was estimated during a meal tolerance test, and a muscle biopsy was obtained to assess muscle lipid accumulation and protein markers associated with insulin resistance, inflammation, and the regulation of lipid metabolism. Whole-body insulin sensitivity declined markedly after 2 weeks of overeating (Matsuda composite index: 8.3 ± 1.3 vs. 4.6 ± 0.7, p < 0.05). However, muscle markers of insulin resistance and inflammation (i.e., phosphorylation of IRS-1-Ser312, Akt-Ser473, and c-Jun N-terminal kinase) were not altered by overeating. Intramyocellular lipids tended to increase after 2 weeks of overeating (triacylglyceride: 7.6 ± 1.6 vs. 10.0 ± 1.8 nmol·mg−1 wet weight; diacylglyceride: 104 ± 10 vs. 142 ± 23 pmol·mg−1 wet weight) but these changes did not reach statistical significance. Overeating induced a 2-fold increase in 24-h insulin response (area under the curve (AUC); p < 0.05), with a resultant ∼35% reduction in 24-h plasma fatty acid AUC (p < 0.05). This chronic reduction in circulating fatty acids may help explain the lack of a robust increase in muscle lipid accumulation. In summary, our findings suggest alterations in skeletal muscle metabolism may not contribute meaningfully to the marked whole-body insulin resistance observed after 2 weeks of overeating.

scholarly journals Hemin Improves Insulin Sensitivity and Lipid Metabolism in Cultured Hepatocytes and Mice Fed a High-Fat Diet

Nutrients ◽  
2017 ◽  
Vol 9 (8) ◽  
pp. 805 ◽  
Author(s):  
Yi Luan ◽  
Fang Zhang ◽  
Yalan Cheng ◽  
Jun Liu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Cultured Hepatocytes ◽  
High Fat

scholarly journals Chronic Dietary Branched-Chain Amino Acids Induced Lipid Oxidation and Blunted Insulin-Stimulated Glucose Production in Mice With NAFLD

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 529-529
Author(s):  
Chaitra Surugihalli ◽  
Vaishna Muralidaran ◽  
Kruti Patel ◽  
Tabitha Gregory ◽  
Nishanth Sunny
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Lipid Oxidation ◽  
Glucose Production ◽  
Branched Chain Amino Acids ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Branched Chain

Abstract Objectives Elevated circulating branched-chain amino acids (BCAAs) during insulin resistance are strong predictors of type 2 diabetes mellitus onset. Defects in BCAA degradation are evident in several tissues during insulin resistance and non-alcoholic fatty liver disease (NAFLD). Furthermore, alterations in BCAA metabolism are associated with changes in several aspects lipid metabolism, including lipogenesis, ketogenesis and mitochondrial TCA cycle activity. Considering the crosstalk between BCAAs and lipid metabolism, we hypothesized that chronic supplementation of BCAAs will modulate hepatic insulin resistance and mitochondrial lipid oxidation during NAFLD. Methods Mice (C57BL/6N) were reared on either a low-fat (LF; 10% fat kcal), high-fat (HF; 60% fat kcal or high-fat diet supplemented with BCAA (HFBA; 150% BCAA) for 24 weeks. Metabolic profiling was conducted under fed or overnight fasted (14–16 hrs) conditions. A subset of overnight fasted mice from the HF and HFBA groups were subjected to hyperinsulinemic euglycemic clamps, following implantation of jugular vein catheters. Results Feeding HF and HFBA diets resulted in NAFLD. Circulating BCAAs were higher in ‘fed’ mice consuming HFBA diet (e.g., Valine, µM ± SEM; 311 ± 38 in HF, 432 ± 34 in HFBA, P ≤ 0.05). Overnight fasting significantly reduced BCAA levels in all groups, but the fasting levels of BCAAs remained similar between groups. Fed-to-fasted fold changes in blood glucose, serum insulin and c-peptide were higher in HFBA mice (P ≤ 0.05). Insulin stimulated suppression of glucose production (% ± SEM; HF = 38 ± 11, HFBA = 16 ± 16) was blunted in HFBA mice.  Furthermore, fed-to-fasted expression of hepatic genes involved in lipid oxidation, including LCAD, MCAD, PPARa and CPT1a were significantly higher (P ≤ 0.05) in the HFBA mice. Conclusions In summary, chronic BCAA supplementation induced hepatic lipid oxidation gene expression, without any apparent improvements in insulin sensitivity. In conclusion, while the induction of lipid oxidation by BCAAs could explain certain beneficial effects associated with their supplementation, the longer-term impact of the BCAAs on insulin sensitivity need to be further explored. Funding Sources National Institutes of Health (NIH) grant RO1-DK-112865

DIURNAL VARIATION IN PLASMA TESTOSTERONE AND CORTISOL IN RHESUS MONKEYS LIVING IN SOCIAL GROUPS

1978 ◽  
Vol 76 (1) ◽  
pp. 67-74 ◽  
Author(s):  
R. M. ROSE ◽  
T. P. GORDON ◽  
I. S. BERNSTEIN
Keyword(s):  
Diurnal Variation ◽  
Individual Variation ◽  
Rhesus Monkeys ◽  
Plasma Cortisol ◽  
Social Groups ◽  
Time Of Day ◽  
Plasma Testosterone ◽  
Diurnal Changes ◽  
Considerable Individual Variation ◽  
Male Rhesus

SUMMARY Concentrations of cortisol and testosterone in the plasma of adult male rhesus monkeys living in social groups were determined during a 27-h period. Capture and venipuncture of experienced, conditioned animals did not lead to a fall in the concentration of testosterone in the plasma during the 90 min immediately after removal from the group. Both plasma cortisol and plasma testosterone concentrations showed a significant fall and rise in samples collected every 3 h during a 27-h period, even though there was considerable individual variation. During the autumn breeding season, animals showed higher concentrations of testosterone at both 10.00 and 22.00 h compared with those observed at the same times during the summer. Even though animals demonstrated significant diurnal changes, testosterone samples withdrawn at the same time of day (10.00 h) on consecutive days were significantly correlated with one another (r = 0·65, n = 27, P < 0·01), suggesting the usefulness of sampling once a day to study potential environmental influences on plasma testosterone concentrations.

Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet

2016 ◽  
Vol 310 (1) ◽  
pp. E32-E40 ◽  
Author(s):  
Saori Kakehi ◽  
Yoshifumi Tamura ◽  
Kageumi Takeno ◽  
Yuko Sakurai ◽  
Minako Kawaguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Gene Set Enrichment Analysis ◽  
Vastus Lateralis Muscle ◽  
Intramyocellular Lipid ◽  
High Fat ◽  
Impaired Insulin ◽  
High Responders

The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by 1H magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated by HFD in the HR group but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR, n = 9; HR, n = 11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle.

scholarly journals 12 Effects of excess iron and dietary fat on lipid metabolism

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 15-16
Author(s):  
Wan Ma
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Iron Status ◽  
Fasting Blood Glucose ◽  
High Fat ◽  
High Iron ◽  
Excess Iron

Abstract Diets rich in fat and energy are associated with metabolic syndrome. Imbalanced systemic iron status has long been epidemiologically associated with obesity-related diseases. The aim of this study is to investigate the interaction between dietary fat and injected iron in the context of glucose and lipid metabolism. C57BL6/J mice were divided into four groups and fed normal chow (NC) and high-fat diet (HFD) with adequate or excess iron for 16 weeks. Excess iron was added by intraperitoneal injection with iron dextran (120 mg/g of body weight) every other week from 4th week (NC+Fe and HFD+Fe), six times in total. The results showed that high iron levels decreased the growth rates of mice without affecting their feed intake. High iron levels increased the adipocyte numbers by 1.6-fold in subcutaneous adipose tissue (SAT) and 3.5-fold in visceral adipose tissue (VAT), while excess iron inhibited their adipocyte hypertrophy. These changes were paralleled by alterations in the levels of enzymes related to hepatic lipid storage and β-oxidation. Especially two key enzymes, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) (P &lt; 0.01) and fat specific protein 27 (FSP27) (P &lt; 0.01) were markedly decreased in iron-treated groups compared with their counterparts. In addition, high iron levels decreased insulin sensitivity by increasing 15% of fasting blood glucose and 23% of insulin levels and the average under curve of intraperitoneal glucose tolerance test (IPGTT) was also decreased (P &lt; 0.05). These results were consistent with the decrease of mRNA expression of enzymes related to hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase 1 (PCK1) (P &lt; 0.05) and fructose-1,6-bisphosphatase 1 (FBP1) (P &lt; 0.05) in iron-treated mice. Thus, high-fat diets and iron overload were associated with insulin resistance, modified lipid deposition and iron metabolism. High iron levels could protect mice from high-fat diet induced obesity by decreasing insulin sensitivity.

scholarly journals Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I-deficient mice

2013 ◽  
Vol 305 (7) ◽  
pp. E834-E844 ◽  
Author(s):  
Fiona C. McGillicuddy ◽  
Clare M. Reynolds ◽  
Orla Finucane ◽  
Eilish Coleman ◽  
Karen A. Harford ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Saturated Fatty Acids ◽  
Interleukin 1 ◽  
Stromal Vascular Fraction ◽  
Metabolic Health ◽  
High Fat

Emerging evidence has demonstrated that saturated fatty acids prime pro-IL-1β production and inflammasome-mediated IL-1β activation is critical in obesity-associated insulin resistance (IR). Nonetheless, IL-1 receptor I-deficient (IL-1RI−/−) mice develop mature-onset obesity despite consuming a low-fat diet (LFD). With this apparent contradiction, the present study evaluated whether IL-1RI−/− mice were protected against long-term (6 mo) high-fat diet (HFD)-induced IR. Male wild-type and IL-1RI−/− mice were fed LFD or HFD for 3 or 6 mo, and glucose and insulin tolerance tests were performed. Adipose insulin sensitivity, cytokine profiles, and adipocyte morphology were assessed. The adipogenic potential of stromal vascular fraction was determined. Hepatic lipid accumulation and insulin sensitivity were characterized. IL-1RI−/− mice developed glucose intolerance and IR after 6 mo HFD compared with 3 mo HFD, coincident with enhanced weight gain, hyperinsulinemia, and hyperleptinemia. The aggravated IR phenotype was associated with loss of adipose functionality, switch from adipocyte hyperplasia to hypertrophy and hepatosteatosis. Induction of adipogenic genes was reduced in IL-1RI−/− preadipocytes after 6 mo HFD compared with 3 mo HFD. Obese LFD-IL-1RI−/− mice exhibited preserved metabolic health. IL-1RI−/− mice develop glucose intolerance and IR after 6 mo HFD intervention. While mature-onset obesity is evident in LFD-IL-1RI−/− mice, the additional metabolic insult of HFD was required to drive adipose inflammation and systemic IR. These findings indicate an important interaction between dietary fat and IL-1, relevant to optimal metabolic health.

Sign in / Sign up

Export Citation Format

Share Document