Possible integrative Actions of Leptin and insulin Signaling in the Hypothalamus Targeting energy Homeostasis

被引:48
作者
Thon, Mina [1 ]
Hosoi, Toru [1 ]
Ozawa, Koichiro [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pharmacotherapy, Hiroshima, Japan
来源
FRONTIERS IN ENDOCRINOLOGY | 2016年 / 7卷
关键词
leptin; insulin; GRP78; leptin resistance; endoplasmic reticulum stress; food intake; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED-PROTEIN RESPONSE; TYROSINE-PHOSPHATASE; 1B; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; BODY-WEIGHT; GLUCOSE-HOMEOSTASIS; DOWN-REGULATION; OBESE GENE; IN-VIVO;
D O I
10.3389/fendo.2016.00138
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Obesity has emerged as one of the most burdensome conditions in modern society. In this context, understanding the mechanisms controlling food intake is critical. At present, the adipocyte-derived hormone leptin and the pancreatic beta-cell-derived hormone insulin are considered the principal anorexigenic hormones. Although leptin and insulin signal transduction pathways are distinct, their regulation of body weight maintenance is concerted. Resistance to the central actions of leptin or insulin is linked to the emergence of obesity and diabetes mellitus. A growing body of evidence suggests a convergence of leptin and insulin intracellular signaling at the insulin-receptor-substrate-phosphatidylinositol-3-kinase level. Moreover, numerous factors mediating the pathophysiology of leptin resistance, a hallmark of obesity, such as endoplasmic reticulum stress, protein tyrosine phosphatase 1B, and suppressor of cytokine signaling 3 also contribute to insulin resistance. Recent studies have also indicated that insulin potentiates leptin-induced signaling. Thus, a greater understanding of the overlapping functions of leptin and insulin in the central nervous system is vital to understand the associated physiological and pathophysiological states. This mini-review focuses on the cross talk and integrative signaling of leptin and insulin in the regulation of energy homeostasis in the brain.
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页数:7
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共 104 条
  • [1] Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity
    Air, EL
    Strowski, MZ
    Benoit, SC
    Conarello, SL
    Salituro, GM
    Guan, XM
    Liu, K
    Woods, SC
    Zhang, BB
    [J]. NATURE MEDICINE, 2002, 8 (02) : 179 - 183
  • [2] Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus
    Baskin, DG
    Breininger, JF
    Schwartz, MW
    [J]. DIABETES, 1999, 48 (04) : 828 - 833
  • [3] INSULIN AND INSULIN-LIKE GROWTH-FACTORS IN THE CNS
    BASKIN, DG
    WILCOX, BJ
    FIGLEWICZ, DP
    DORSA, DM
    [J]. TRENDS IN NEUROSCIENCES, 1988, 11 (03) : 107 - 111
  • [4] STAT3 signalling is required for leptin regulation of energy balance but not reproduction
    Bates, SH
    Stearns, WH
    Dundon, TA
    Schubert, M
    Tso, AWK
    Wang, YP
    Banks, AS
    Lavery, HJ
    Haq, AK
    Maratos-Flier, E
    Neel, BG
    Schwartz, MW
    Myers, MG
    [J]. NATURE, 2003, 421 (6925) : 856 - 859
  • [5] SATURABLE TRANSPORT OF INSULIN FROM PLASMA INTO THE CENTRAL-NERVOUS-SYSTEM OF DOGS IN-VIVO - A MECHANISM FOR REGULATED INSULIN DELIVERY TO THE BRAIN
    BAURA, GD
    FOSTER, DM
    PORTE, D
    KAHN, SE
    BERGMAN, RN
    COBELLI, C
    SCHWARTZ, MW
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (04) : 1824 - 1830
  • [6] Neuronal PTP1B regulates body weight, adiposity and leptin action
    Bence, Kendra K.
    Delibegovic, Mirela
    Xue, Bingzhong
    Gorgun, Cem Z.
    Hotamisligil, Gokhan S.
    Neel, Benjamin G.
    Kahn, Barbara B.
    [J]. NATURE MEDICINE, 2006, 12 (08) : 917 - 924
  • [7] Cross down-regulation of leptin and insulin receptor expression and signalling in a human neuronal cell line
    Benomar, Y
    Roy, AF
    Aubourg, A
    Djiane, J
    Taouis, M
    [J]. BIOCHEMICAL JOURNAL, 2005, 388 : 929 - 939
  • [8] Divergent signaling capacities of the long and short isoforms of the leptin receptor
    Bjorbaek, C
    Uotani, S
    da Silva, B
    Flier, JS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (51) : 32686 - 32695
  • [9] Identification of SOCS-3 as a potential mediator of central leptin resistance
    Bjorbaek, C
    Elmquist, JK
    Frantz, JD
    Shoelson, SE
    Flier, JS
    [J]. MOLECULAR CELL, 1998, 1 (04) : 619 - 625
  • [10] Obesity and Free Fatty Acids
    Boden, Guenther
    [J]. ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA, 2008, 37 (03) : 635 - +