Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain

Benjamin Anderschou Holbech Jensen; Thomas Svava Nielsen; Andreas Mæchel Fritzen; Jacob Bak Holm; Even Fjære; Annette Karen Lundbeck Serup; Kamil Borkowski; Steve Risis; Simone I. Pærregaard; Ida Søgaard; Audrey Angélique G Poupeau; Michelle Poulsen; Tao Ma; Christian Sina; Bente Kiens; Lise Madsen; Karsten Kristiansen; Jonas Thue Treebak

doi:10.1016/j.metabol.2016.09.002

Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain

Benjamin Anderschou Holbech Jensen, Thomas Svava Nielsen, Andreas Mæchel Fritzen, Jacob Bak Holm, Even Fjære, Annette Karen Lundbeck Serup, Kamil Borkowski, Steve Risis, Simone I. Pærregaard, Ida Søgaard, Audrey Angélique G Poupeau, Michelle Poulsen, Tao Ma, Christian Sina, Bente Kiens, Lise Madsen, Karsten Kristiansen, Jonas Thue Treebak

18 Citations (Scopus)

79 Downloads (Pure)

Abstract

BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota.

METHODS: We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment.

RESULTS: Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum.

CONCLUSIONS: Intake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion.

Original language	English
Journal	Metabolism
Volume	65
Issue number	12
Pages (from-to)	1706-1719
Number of pages	14
ISSN	0026-0495
DOIs	https://doi.org/10.1016/j.metabol.2016.09.002
Publication status	Published - 1 Dec 2016

Keywords

Faculty of Science
Intestinal epithelial cells
Weight stability
Gut microbiota
Feeding behavior
Endogenous glucose production

Access to Document

10.1016/j.metabol.2016.09.002Licence: CC BY-NC-ND

Jensen_2016_Dietary_fatFinal published version, 1.59 MBLicence: CC BY-NC-ND

Cite this

Jensen, B. A. H., Nielsen, T. S., Fritzen, A. M., Holm, J. B., Fjære, E., Serup, A. K. L., Borkowski, K., Risis, S., Pærregaard, S. I., Søgaard, I., Poupeau, A. A. G., Poulsen, M., Ma, T., Sina, C., Kiens, B., Madsen, L., Kristiansen, K., & Treebak, J. T. (2016). Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain. Metabolism, 65(12), 1706-1719. https://doi.org/10.1016/j.metabol.2016.09.002

Jensen, BAH , Nielsen, TS , Fritzen, AM, Holm, JB, Fjære, E, Serup, AKL, Borkowski, K, Risis, S, Pærregaard, SI, Søgaard, I, Poupeau, AAG, Poulsen, M, Ma, T, Sina, C, Kiens, B, Madsen, L, Kristiansen, K & Treebak, JT 2016, 'Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain', Metabolism, vol. 65, no. 12, pp. 1706-1719. https://doi.org/10.1016/j.metabol.2016.09.002

@article{0379dfa731aa4ec9a7c3453d0cdfddd3,

title = "Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain",

abstract = "BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota.METHODS: We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment.RESULTS: Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum.CONCLUSIONS: Intake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion.",

keywords = "Faculty of Science, Intestinal epithelial cells, Weight stability, Gut microbiota, Feeding behavior, Endogenous glucose production",

author = "Jensen, {Benjamin Anderschou Holbech} and Nielsen, {Thomas Svava} and Fritzen, {Andreas M{\ae}chel} and Holm, {Jacob Bak} and Even Fj{\ae}re and Serup, {Annette Karen Lundbeck} and Kamil Borkowski and Steve Risis and P{\ae}rregaard, {Simone I.} and Ida S{\o}gaard and Poupeau, {Audrey Ang{\'e}lique G} and Michelle Poulsen and Tao Ma and Christian Sina and Bente Kiens and Lise Madsen and Karsten Kristiansen and Treebak, {Jonas Thue}",

note = "CURIS 2016 NEXS 325",

year = "2016",

month = dec,

day = "1",

doi = "10.1016/j.metabol.2016.09.002",

language = "English",

volume = "65",

pages = "1706--1719",

journal = "Metabolism",

issn = "0026-0495",

publisher = "Elsevier",

number = "12",

}

TY - JOUR

T1 - Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain

AU - Jensen, Benjamin Anderschou Holbech

AU - Nielsen, Thomas Svava

AU - Fritzen, Andreas Mæchel

AU - Holm, Jacob Bak

AU - Fjære, Even

AU - Serup, Annette Karen Lundbeck

AU - Borkowski, Kamil

AU - Risis, Steve

AU - Pærregaard, Simone I.

AU - Søgaard, Ida

AU - Poupeau, Audrey Angélique G

AU - Poulsen, Michelle

AU - Ma, Tao

AU - Sina, Christian

AU - Kiens, Bente

AU - Madsen, Lise

AU - Kristiansen, Karsten

AU - Treebak, Jonas Thue

N1 - CURIS 2016 NEXS 325

PY - 2016/12/1

Y1 - 2016/12/1

N2 - BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota.METHODS: We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment.RESULTS: Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum.CONCLUSIONS: Intake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion.

AB - BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota.METHODS: We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment.RESULTS: Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum.CONCLUSIONS: Intake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion.

KW - Faculty of Science

KW - Intestinal epithelial cells

KW - Weight stability

KW - Gut microbiota

KW - Feeding behavior

KW - Endogenous glucose production

U2 - 10.1016/j.metabol.2016.09.002

DO - 10.1016/j.metabol.2016.09.002

M3 - Journal article

C2 - 27832859

SN - 0026-0495

VL - 65

SP - 1706

EP - 1719

JO - Metabolism

JF - Metabolism

IS - 12

ER -

Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain

Abstract

Keywords

Access to Document

Fingerprint

Cite this