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Science Behind IF and Keto

Scientific Studies For Your Pleasure

If you are anything like me, you love to get the actual source of things. I found early on that love reading the actual data and do not really trust most peoples interpretation of it, simply because these days they have their own agenda which is usually trying to sell you something. 🙂 

So when I can, I will post the sources that I use here.  I will always make sure I make this free and anyone can come here. 

For now, it is going to be just an info dump. One of these days I may cataloged.  In the meantime, have fun and hope this helps.  

If you have reliable information source, please feel to let me know in the comments below and I will do my best to add it here based on the accuracy of the source.

This portion below is on the impact of insulin and is borrowed from Ivor Cummings.

A non-complete selection of papers referenced in preparing this content with Gabor Erdosi’s help (he dug out a lot of ’em!):Imbalanced insulin action in chronic over nutrition:

Clinical harm, molecular mechanisms, and a way forward Atherosclerosis 247 (2016) 225e282 Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009 Diabetologia (2010) 53:1270–1287 Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production Titchenell et al., 2016, Cell Metabolism 23, 1–13SULF2 Strongly Predisposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus Obesity (Silver Spring). 2014 May ; 22(5): 1309–1316. SULF-2: AN EXTRACELLULAR MODULATOR OF CELL SIGNALING AND A CANCER TARGET CANDIDATE Expert Opin Ther Targets. 2010 September ; 14(9): 935–949. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose Biological Reviews 91 (2016) 452–468PKC-θ knockout mice are protected from fat-induced insulin resistance     J. Clin. Invest. 114:823–827 (2004).Protein kinase Cdeficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodelingJournal of Lipid Research Volume 53, 2012Inhibition of PKC¯ Improves Glucocorticoid-Induced Insulin Resistance in Rat AdipocytesLife, 54: 365–370, 2002Obesity and insulin resistanceThe Journal of Clinical Investigation | August 2000 | Volume 106 | Number 4Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes molecular cell biology volume 9May 2008 Increased glucose uptake promotes oxidative stress and PKC- activation in adipocytes of obese, insulin-resistant mice Am J Physiol Endocrinol Metab 285: E295–E302, 2003Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver NATURE |VOL 409 | 8 FEBRUARY 2001 |www.nature.comDisruption of Adipose Rab10-Dependent Insulin Signaling Causes Hepatic Insulin Resistance Diabetes Publish Ahead of Print, published online March 25, 2016A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism 9A P R I L2 0 1 2   VO L 4 8 4   N AT U R ENormal muscle glucose uptake in mice deficient in muscle GLUT4 Journal of Endocrinology (2012) 214, 313–327Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism NATURE COMMUNICATIONS | 7:11365 | DOI: 10.1038/ncomms11365De novo lipogenesis in human fat and liver is linked to ChREBP-b and metabolic health NATURE COMMUNICATIONS | 4:1528 | DOI: 10.1038/ncomms2537 | of Adipose Tissue Fatty Acid Trafficking in Obesity A Driver for Ectopic Fat Deposition? DIABETES, VOL. 60, JANUARY 2011 Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men 9 September 2015 Vol 7 Issue 304 304re7GLUT4 Expression in Adipocytes Regulates De Novo Lipogenesis and Levels of a Novel Class of Lipids With Antidiabetic and Anti-inflammatory Effects Diabetes 2016;65:1808–1815Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism Cell. 2008 September 19; 134(6): 933–944.Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*  THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 25, pp. 21492–21500, June 15, 2012Insulin Resistance – A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease DIABETES CARE, VOL. 14, NO. 3, MARCH 1991Excess exposure to insulin may be the primary cause of insulin resistance Am J Physiol Endocrinol Metab 298: E372, 2010Excess exposure to insulin (glargine) induces type 2 diabetes mellitus in mice on chow diet. Journal of Endocrinology (2014) 221, 469–480Skeletal Muscle Insulin Resistance in Normoglycemic Subjects With a Strong Family History of Type 2 Diabetes Is Associated With Decreased Insulin-Stimulated Insulin Receptor Substrate-1 Tyrosine Phosphorylation DIABETES, VOL. 50, NOVEMBER 2001Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes Nat Rev Mol Cell Biol. 2008 May ; 9(5): 367–377.Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cellsHammarstedt et al. Diabetology & Metabolic Syndrome 2012, 4:42Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance—is insulin resistance initiated in the adipose tissue? International Journal of Obesity (2002) 26, 897–904Arachidonic acid has a dominant effect to regulate lipogenic genes in 3T3-L1 adipocytes compared to omega-3 fatty acidsFood & Nutrition Research 2015, 59: 25866Omega-6 polyunsaturated fatty acids and the early origins of obesity Curr Opin Endocrinol Diabetes Obes 2013, 20:56–61The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux J Clin Invest. 2016;126(1):12–22.Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 DiabetesPerry et al., 2015, Cell 160, 1–14Insulin-independent regulation of hepatic triglyceride synthesis by fatty acidsPNAS | January 27, 2015 | vol. 112 | no. 4 | 1143–1148Plasma non-esterified fatty acids: why are we not measuring them routinely? Ann Clin Biochem 2005; 42: 413–414Impaired Free Fatty Acid Suppression During Hyperinsulinemia Is a Characteristic Finding in Familial Combined Hyperlipidemia, but Insulin Resistance Is Observed Only in Hypertriglyceridemic Patients Arterioscler Thromb Vasc Biol. 2000;20:164-170.)Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production Titchenell et al., 2016, Cell Metabolism 23, 1–13Glucose and Free Fatty Acid Metabolism in Non-insulin-dependent Diabetes Mellitus   J. Clin. Invest. Volume 84, July 1989, 205-213The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjectsJ. Clin. Invest. 103:365–372 (1999).Effects of Free Fatty Acid Elevation on Postabsorptive Endogenous Glucose Production and Gluconeogenesis in Humans DIABETES, VOL. 49, MAY 2000Effects of Free Fatty Acids Per Se on Glucose Production, Gluconeogenesis, and Glycogenolysis  DIABETES, VOL. 52, FEBRUARY 2003Free Fatty Acid as a link in the Regulation of Hepatic Glucose Output by Peripheral InsulinDIABETES, VOL. 44, SEPTEMBER 1995 Stearoyl-CoA desaturase and insulin signaling — What is the molecular switch? Biochimica et Biophysica Acta 1797 (2010) 1189–1194Hepatic lipogenesis independent of insulin in type 2 diabetes mellitus—a paradox clarifiedProc. Natl Acad. Sci. USA doi:10.1073/pnas.1423952112 Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise TrainingCompr Physiol. 2013 January ; 3(1): 1–58.Lipid-Induced Insulin Resistance in Skeletal Muscle: The Chase for the Culprit Goes from Total Intramuscular Fat to Lipid Intermediates, and Finally to Species of Lipid IntermediatesNutrients 2016, 8, 466Fatty Acids, Obesity, and Insulin Resistance: Time for a ReevaluationDIABETES, VOL. 60, OCTOBER 2011Impaired (‘diabetic’) insulin signaling and action occur in fat cells long before glucose intolerance—is insulin resistance initiated in the adipose tissue? International Journal of Obesity (2002) 26, 897 – 904


























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28.   Cakir-Atabek, H., Demir, S., Pinarbassili, R., Bunduz, N. Effects of Different Resistance Training Intensity on Indices of Oxidative Stress. Journal of Strength and Conditioning Research. September 2010. 24(9), 2491-2498.)

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35.   Johnstone AM, et al. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. The American Journal of Clinical Nutrition, 2008.

36.   Source: Samaha FF, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine, 2003.




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68.   Halagappa VK, Neurobiol Dis. 2007 Apr;26(1):212-20. Epub 2007 Jan 13. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease.

69.   Live longer –, and














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