The citrus flavonoids hesperetin and naringenin block the lipolytic actions of TNF-alpha in mouse adipocytes.
Obese adipose tissue is characterized by an excessive production of inflammatory adipokines including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha stimulates free fatty acid (FFA) secretion through adipocyte lipolysis, and increased plasma levels of FFA promote insulin resistance. In this report, we show that hesperetin and naringenin, two citrus flavonoids, inhibit TNF-alpha-stimulated FFA secretion from mouse adipocytes. These flavonoids block the TNF-alpha-induced activation of the NF-kappaB and ERK pathways. Moreover, hesperetin and naringenin prevent TNF-alpha from downregulating the transcription of two antilipolytic genes, perilipin and PDE3B. These effects are mediated through the inhibition of the ERK pathway. In contrast, the inhibition of the NF-kappaB pathway by hesperetin and naringenin suppresses the transcription of IL-6, which induces FFA secretion in an autocrine manner. Our results provide novel evidence that hesperetin and naringenin directly inhibit TNF-alpha-stimulated FFA secretion. These findings may be useful for ameliorating FFA-induced insulin resistance.
Yoshida
Hiroki
H
Second Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka City, Miyazaki 882-8508, Japan. h-yoshida@phoenix.ac.jp
Takamura
Norito
N
Shuto
Tsuyoshi
T
Ogata
Kenji
K
Tokunaga
Jin
J
Kawai
Keiichi
K
Kai
Hirofumi
H
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002957:Citrus / Q000737:chemistry*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006569:Hesperidin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D044950:Flavanones; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D006569:Hesperidin; C005273:naringenin; C013015:hesperetin