Fenretinide ameliorates insulin resistance and fatty liver in obese mice

In Uk Koh, Hye Seung Jun, Joo Sun Choi, Joo Hyun Lim, Won Ho Kim, Jong-Bok Yoon, Jihyun Song

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Fenretinide (FEN), a ligand of retinol binding protein 4 (RBP4), has been suggested as a measure to reduce insulin resistance and its associated disorders such as obesity, and fatty liver by reducing serum RBP4. We investigated whether there is another possible mechanism by which fenretinide reduces insulin resistance and fatty liver in genetically obese (ob/ob) mice. Male obese mice fed a high-fat diet (45% of calories from fat) were divided into two groups (n=13 each). One (FEN) received fenretinide (20 mg/kg body weight, intraperitoneally) and the other (O) received vehicle three times weekly for 24 d. C57BL/6J mice fed a normal-fat diet (16% of calories from fat) were used as a control (C; n=13). No changes in fat weight and serum leptin level could be observed in FEN mice. Lower plasma RBP4 was observed in FEN mice compared with O mice. Fenretinide improved whole-body insulin sensitivity based on glucose and insulin tolerance tests and the homeostasis model assessment of insulin resistance. Fenretinide decreased the plasma lipid (triglyceride, cholesterol, and free-fatty acid) levels, hepatic TG level, and histological steatosis score. The mechanism by which fenretinide prevents fatty liver may be explained by an increased plasma adiponectin level, increased activation of hepatic AMP-activated protein kinase, and the expression of peroxisome proliferator-activated protein-α and peroxisomal acyl-CoA oxidase, which promote fat oxidation. FEN alleviated insulin resistance and fatty liver in obese mice and thus may act as an anti-lipidemic and anti-diabetic drug.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume35
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

Fingerprint

Fenretinide
Obese Mice
Fatty Liver
Insulin Resistance
Fats
Retinol-Binding Proteins
Plasma Retinol-Binding Proteins
Peroxisome Proliferators
AMP-Activated Protein Kinases
Liver
Adiponectin
High Fat Diet
Glucose Tolerance Test
Leptin
Serum
Inbred C57BL Mouse
Nonesterified Fatty Acids
Triglycerides
Homeostasis
Obesity

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Koh, In Uk ; Jun, Hye Seung ; Choi, Joo Sun ; Lim, Joo Hyun ; Kim, Won Ho ; Yoon, Jong-Bok ; Song, Jihyun. / Fenretinide ameliorates insulin resistance and fatty liver in obese mice. In: Biological and Pharmaceutical Bulletin. 2012 ; Vol. 35, No. 3. pp. 369-375.
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Fenretinide ameliorates insulin resistance and fatty liver in obese mice. / Koh, In Uk; Jun, Hye Seung; Choi, Joo Sun; Lim, Joo Hyun; Kim, Won Ho; Yoon, Jong-Bok; Song, Jihyun.

In: Biological and Pharmaceutical Bulletin, Vol. 35, No. 3, 01.03.2012, p. 369-375.

Research output: Contribution to journalArticle

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AU - Koh, In Uk

AU - Jun, Hye Seung

AU - Choi, Joo Sun

AU - Lim, Joo Hyun

AU - Kim, Won Ho

AU - Yoon, Jong-Bok

AU - Song, Jihyun

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