Small amounts of dietary medium-chain fatty acids protect against insulin resistance during caloric excess in humans

Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a three-day hypercaloric high-fat diet (+75% energy, 81-83E% fat) in randomized order. For one group (n=8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n=9) ingested a matched diet, but with ~30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated LCFAs. A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal FA oxidation, maintained glucose metabolic flexibility, increased non-oxidative glucose disposal related to lower starting glycogen content and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.

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Medium-chain fatty acids ameliorate insulin resistance caused by high-fat diets in rats

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.925 ◽

2009 ◽

Vol 25 (2) ◽

pp. 185-194 ◽

Cited By ~ 35

Author(s):

Silvia Wein ◽

Siegfried Wolffram ◽

Jürgen Schrezenmeir ◽

Daniela Gašperiková ◽

Iwar Klimeš ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

High Fat ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

High Fat Diets ◽

Fat Diets ◽

Ameliorate Insulin Resistance ◽

Chain Fatty Acids

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Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2011-1884 ◽

2012 ◽

Vol 97 (1) ◽

pp. 208-216 ◽

Cited By ~ 19

Author(s):

Joris Hoeks ◽

Marco Mensink ◽

Matthijs K. C. Hesselink ◽

Kim Ekroos ◽

Patrick Schrauwen

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fat Accumulation ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Induce Insulin Resistance ◽

Chain Fatty Acids

Context: Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling. Objective: We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance. Design and Methods: Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp. Results: MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (−28%, P = 0.003) and MCT/LCT (−20%, P < 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered. Conclusions: Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.

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Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans

Diabetes ◽

10.2337/db20-0582 ◽

2020 ◽

Vol 70 (1) ◽

pp. 91-98

Author(s):

Anne-Marie Lundsgaard ◽

Andreas M. Fritzen ◽

Kim A. Sjøberg ◽

Maximilian Kleinert ◽

Erik A. Richter ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Caloric Excess ◽

Chain Fatty Acids

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Using Dictyostelium to Advance Our Understanding of the Role of Medium Chain Fatty Acids in Health and Disease

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.722066 ◽

2021 ◽

Vol 9 ◽

Author(s):

Erwann Pain ◽

Sonia Shinhmar ◽

Robin S. B. Williams

Keyword(s):

Fatty Acids ◽

Molecular Mechanisms ◽

Medium Chain Triglyceride ◽

Decanoic Acid ◽

High Fat ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Ketogenic Diets ◽

Health And Disease ◽

Chain Fatty Acids

Ketogenic diets have been utilized for many years to improve health, and as a dietary approach for the treatment of a range of diseases, where the mechanism of these low carbohydrate and high fat diets is widely considered to be through the production of metabolic products of fat breakdown, called ketones. One of these diets, the medium chain triglyceride ketogenic diet, involves high fat dietary intake in the form of medium chain fatty acids (MCFAs), decanoic and octanoic acid, and is commonly used in endurance and high intensity exercises but has also demonstrated beneficial effects in the treatment of numerous pathologies including drug resistant epilepsy, cancer, and diabetes. Recent advances, using Dictyostelium discoideum as a model, have controversially proposed several direct molecular mechanisms for decanoic acid in this diet, independent of ketone generation. Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). These discoveries could potentially impact the treatment of a range of disorders including epilepsy, cancer and bipolar disorder. In this review, we summarize the newly proposed mechanisms for decanoic acid, identified using D. discoideum, and highlight potential roles in health and disease treatment.

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Enhanced Bioavailability of Curcumin Nanoemulsions Stabilized with Phosphatidylcholine Modified with Medium Chain Fatty Acids

Current Drug Delivery ◽

10.2174/1567201813666160919142811 ◽

2017 ◽

Vol 14 (3) ◽

pp. 377-385 ◽

Cited By ~ 8

Author(s):

Angelica A. Ochoa-Flores ◽

Josafat A. Hernández-Becerra ◽

Adriana Cavazos-Garduño ◽

Ida Soto-Rodríguez ◽

Maria Guadalupe Sanchez-Otero ◽

...

Keyword(s):

Fatty Acids ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Chain Fatty Acids

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Effects of ketogenic diet containing medium-chain fatty acids on serum inflammatory factor and mTOR signaling pathway in rats

Chemical and Biological Technologies in Agriculture ◽

10.1186/s40538-020-00194-4 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Huan Liu ◽

Jingwei Huang ◽

Hui Liu ◽

Feng Li ◽

Quansheng Peng ◽

...

Keyword(s):

Fatty Acids ◽

Caloric Restriction ◽

Ketogenic Diet ◽

Mtor Pathway ◽

Inflammatory Factor ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Sd Rats ◽

Anti Inflammatory ◽

Chain Fatty Acids

Abstract Background The ketogenic diet (KD) can promote the anti-inflammatory metabolic state and increase ketone body level in rats. This study was to explore the effects and differences of KD with or without medium-chain fatty acids (MCFAs) on serum inflammatory factors and mTOR pathway in Sprague–Dawley (SD) rats. Results Male SD rats were assigned to five groups: control diet (C), 20% caloric restriction diet (LC), 20% caloric restriction ketogenic diet (containing MCFAs) (LCKD1), 20% caloric restriction ketogenic diet (LCKD2) and 20% caloric restriction foreign ketogenic diet (LCKD3), and fed for 30 d. LC and KD could significantly reduce the body weight of rats; LC and KD containing MCFAs showed anti-inflammatory effects; KD without MCFAs decreased the concentration of mTOR1, while KD containing MCFAs decreased the expression of AMPK, mtor1 and P70sk. Conclusions KD containing MCFAs showed better effects on the mTOR pathway and anti-inflammation than that without MCFAs.

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Time course of insulin resistance associated with feeding dogs a high-fat diet

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.272.1.e147 ◽

1997 ◽

Vol 272 (1) ◽

pp. E147-E154 ◽

Cited By ~ 13

Author(s):

A. P. Rocchini ◽

P. Marker ◽

T. Cervenka

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Glucose Uptake ◽

Dose Response ◽

High Fat Diet ◽

Time Course ◽

Rapid Development ◽

Diet Group ◽

Whole Body ◽

High Fat

The current study evaluated both the time course of insulin resistance associated with feeding dogs a high-fat diet and the relationship between the development of insulin resistance and the increase in blood pressure that also occurs. Twelve adult mongrel dogs were chronically instrumented and randomly assigned to either a control diet group (n = 4) or a high-fat diet group (n = 8). Insulin resistance was assessed by a weekly, single-dose (2 mU.kg-1.min-1) euglycemic-hyperinsulinemic clamp on all dogs. Feeding dogs a high-fat diet was associated with a 3.7 +/- 0.5 kg increase in body weight, a 20 +/- 4 mmHg increase in mean blood pressure, a reduction in insulin-mediated glucose uptake [(in mumol-kg-1.min-1) decreasing from 72 +/- 6 before to 49 +/- 7 at 1 wk, 29 +/- 3 at 3 wk, and 30 +/- 2 at 6 wk of the high-fat diet, P < 0.01]. and a reduced insulin-mediated increase in cardiac output. In eight dogs (4 high fat and 4 control), the dose-response relationship of insulin-induced glucose uptake also was studied. The whole body glucose uptake dose-response curve was shifted to the right, and the rate of maximal whole body glucose uptake was significantly decreased (P < 0.001). Finally, we observed a direct relationship between the high-fat diet-induced weekly increase in mean arterial pressure and the degree to which insulin resistance developed. In summary, the current study documents that feeding dogs a high-fat diet causes the rapid development of insulin resistance that is the result of both a reduced sensitivity and a reduced responsiveness to insulin.

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