Deficiency of ER Ca2+ sensor STIM1 in AgRP neurons confers protection against dietary obesity

AbstractVisceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.

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Sensory and postingestional components of palatability in dietary obesity: A review

Appetite ◽

10.1016/0195-6663(89)90076-7 ◽

1989 ◽

Vol 12 (1) ◽

pp. 72

Author(s):

Michael Naim ◽

Morley R. Kare

Keyword(s):

Dietary Obesity

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Reduction of dietary obesity in aP2-Ucp transgenic mice: physiology and adipose tissue distribution

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.5.e768 ◽

1996 ◽

Vol 270 (5) ◽

pp. E768-E775 ◽

Cited By ~ 19

Author(s):

J. Kopecky ◽

Z. Hodny ◽

M. Rossmeisl ◽

I. Syrovy ◽

L. P. Kozak

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Transgenic Mice ◽

Body Weight Gain ◽

Uncoupling Protein ◽

Gene Promoter ◽

Lipid Binding ◽

Brown Fat ◽

Mitochondrial Uncoupling ◽

Dietary Obesity

We seek to determine whether increased energy dissipation in adipose tissue can prevent obesity. Transgenic mice with C57BL6/J background and the adipocyte lipid-binding protein (aP2) gene promoter directing expression of the mitochondrial uncoupling protein (UCP) gene in white and brown fat were used. Physiologically, UCP is essential for nonshivering thermogenesis in brown fat. Mice were assigned to a chow or a high-fat (HF) diet at 3 mo of age. Over the next 25 wk, gains of body weight were similar in corresponding subgroups (n = 6-8) of female and male mice: 4-5 g in chow nontransgenic and transgenic, 20 g in HF nontransgenic, and 9-11 g in HF transgenic mice. The lower body weight gain in the HF transgenic vs. nontransgenic mice corresponded to a twofold lower feed efficiency. Gonadal fat was enlarged, but subcutaneous white fat was decreased in the transgenic vs. nontransgenic mice in both dietary conditions. The results suggest that UCP synthesized from the aP2 gene promoter is capable of reducing dietary obesity.

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Early weight gain and behavioral responsivity as predictors of dietary obesity in rats

Physiology & Behavior ◽

10.1016/0031-9384(83)90175-0 ◽

1983 ◽

Vol 30 (5) ◽

pp. 763-770 ◽

Cited By ~ 19

Author(s):

M HARRINGTON ◽

D COSCINA

Keyword(s):

Weight Gain ◽

Early Weight Gain ◽

Dietary Obesity

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Effect of Environmental Temperature on Dietary Obesity in Osborne-Mendel Rats

Annals of Nutrition and Metabolism ◽

10.1159/000177486 ◽

1988 ◽

Vol 32 (5-6) ◽

pp. 340-346 ◽

Cited By ~ 2

Author(s):

M. Goubern ◽

M.C. Laury ◽

M. Razanoelina ◽

R. Portet

Keyword(s):

Environmental Temperature ◽

Dietary Obesity

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Exercise, dietary obesity, and growth in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1977.232.1.r38 ◽

1977 ◽

Vol 232 (1) ◽

pp. R38-R44 ◽

Cited By ~ 6

Author(s):

G. C. Pitts ◽

L. S. Bull

Keyword(s):

Body Size ◽

High Fat Diet ◽

Treadmill Exercise ◽

Rank Order ◽

Live Weight ◽

Exponential Model ◽

Male Rats ◽

High Fat ◽

Dietary Obesity ◽

Free Body

Four regimens: high-fat diet, exercised (I); chow, exercised (II); high-fat sedentary (III); and chow, sedentary (IV) were initiated in 35-day-old male rats. Growth was exponential in I and II and exponential progressing to rectilinear in III and IV. The exponential model predicted the decreasing rank order in asymptotic weight to be: III, IV, I, II. Body composition data (9 components) showed rank order in masses of fat and the fat-free body mass compartment (FFBM) to be the same as for asymptotic live weight. The rectilinear growth mode probably reflected fat accretion. High-fat diet increased and treadmill exercise decreased FFBM, the latter being reversible. These effects depended on regimen initiations by the 5-7th wk of age. During growth, masses of H2O, muscle, and skin increased as functions of body size; bone as a function of age; and heart, liver, gut, testevity, and diet. Growth in body size was expressed more precisely with FFBM, instead of live weight, as the index of size.

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