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

Fiona C McGillicuddy, Clare M Reynolds, Orla Finucane, Eilish Coleman, Karen A Harford, Christine Grant, Domenico Sergi, Lynda M Williams, Kingston H G Mills, Helen M Roche

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)E834-E844
Number of pages12
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume305
Issue number7
DOIs
Publication statusPublished - 1 Oct 2013

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Glucose Intolerance
High Fat Diet
Insulin Resistance
Fat-Restricted Diet
Interleukin-1
Obesity
Adipocytes
Inflammasomes
Interleukin-1 Receptors
mouse IL1R1 protein
Dietary Fats
Health
Hyperinsulinism
Glucose Tolerance Test
Hypertrophy
Weight Gain
Hyperplasia
Blood Vessels
Fatty Acids
Insulin

Keywords

  • Adipose Tissue
  • Adiposity
  • Animals
  • Diet, High-Fat
  • Dietary Fats
  • Fatty Liver
  • Glucose Intolerance
  • Glucose Tolerance Test
  • Inflammation
  • Insulin
  • Insulin Resistance
  • Leptin
  • Male
  • Mice
  • Mice, Knockout
  • Receptors, Interleukin-1 Type I

Cite this

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. / McGillicuddy, Fiona C; Reynolds, Clare M; Finucane, Orla; Coleman, Eilish; Harford, Karen A; Grant, Christine; Sergi, Domenico; Williams, Lynda M; Mills, Kingston H G; Roche, Helen M.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 305, No. 7, 01.10.2013, p. E834-E844.

Research output: Contribution to journalArticle

McGillicuddy, Fiona C ; Reynolds, Clare M ; Finucane, Orla ; Coleman, Eilish ; Harford, Karen A ; Grant, Christine ; Sergi, Domenico ; Williams, Lynda M ; Mills, Kingston H G ; Roche, Helen M. / 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. In: American Journal of Physiology: Endocrinology and Metabolism. 2013 ; Vol. 305, No. 7. pp. E834-E844.
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AU - McGillicuddy, Fiona C

AU - Reynolds, Clare M

AU - Finucane, Orla

AU - Coleman, Eilish

AU - Harford, Karen A

AU - Grant, Christine

AU - Sergi, Domenico

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AU - Mills, Kingston H G

AU - Roche, Helen M

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AB - 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.

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KW - Adiposity

KW - Animals

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KW - Fatty Liver

KW - Glucose Intolerance

KW - Glucose Tolerance Test

KW - Inflammation

KW - Insulin

KW - Insulin Resistance

KW - Leptin

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Receptors, Interleukin-1 Type I

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JF - American Journal of Physiology: Endocrinology and Metabolism

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