Dataset Information

Mechanisms preserving insulin action during high dietary fat intake in healthy men

ABSTRACT: Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy men ingested saturated (SFA) or poly unsaturated (PUFA) fat-rich diets for six weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with PUFA. In mice, eucaloric feeding of human PUFA and SFA diets lowered hepatic triacylglycerol content compared to low-fat fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Mario Oroshi

LAB HEAD: Bente Kiens

PROVIDER: PXD010516 | Pride | 2018-10-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20170602_QEp1_Easy12-11_SoDo_SA_SAP-PUFA-mice-1.raw	Raw
	20170602_QEp1_Easy12-11_SoDo_SA_SAP-PUFA-mice-1_170603003824.raw	Raw
	20170602_QEp1_Easy12-11_SoDo_SA_SAP-PUFA-mice-3.raw	Raw
	20170602_QEp1_Easy12-11_SoDo_SA_SAP-PUFA-mice-3_170603014551.raw	Raw
	20170602_QEp1_Easy12-11_SoDo_SA_SAP-PUFA-mice-3b.raw	Raw

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Mechanisms Preserving Insulin Action during High Dietary Fat Intake.

Lundsgaard Anne-Marie AM Holm Jacob B JB Sjøberg Kim A KA Bojsen-Møller Kirstine N KN Myrmel Lene S LS Fjære Even E Jensen Benjamin A H BAH Nicolaisen Trine S TS Hingst Janne R JR Hansen Sine L SL Doll Sophia S Geyer Philip E PE Deshmukh Atul S AS Holst Jens J JJ Madsen Lise L Kristiansen Karsten K Wojtaszewski Jørgen F P JFP Richter Erik A EA Kiens Bente B

Cell metabolism 20180927 1

Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy, slightly overweight men ingested saturated or polyunsaturated fat-rich diets for 6 weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diet ...[more]

PMID: 30269983

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Project description:High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. Adult male Wistar rats were fed diets with varying amounts of protein, carbohydrates and fat for 5 weeks. At the end of the experiment, rats were killed and tanscriptome analysis was performed on pooled liver samples.