Mouse Betaine-HomocysteineS-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

Previously, we have shown that intervention by the addition of the citrus flavonoid naringenin to a chow diet enhances the reversal of diet-induced metabolic dysregulation, obesity, and atherosclerosis. However, the metabolic effects of naringenin in the absence of obesity and metabolic dysregulation are unknown. In the present study, we assessed the effect of naringenin supplementation to a chow diet on plasma lipids, adiposity, respiratory exchange ratio (RER), ambulatory activity and tissue lipolysis. For 8 weeks, Ldlr -/- mice were fed an isoflavone-free chow diet supplemented with or without 3% naringenin. Over 8 weeks, there was no difference in caloric intake between the two groups. Naringenin supplementation reduced plasma VLDL-cholesterol (C) (-46%; P <0.05), VLDL-triglycerides (-43%; P <0.05), and LDL-C (-27%; P <0.05) compared to mice consuming chow alone. Chow-fed mice maintained body weight, whereas mice fed chow with naringenin were ~1.4 g lighter ( P <0.05) with significantly reduced adiposity (-48%; P <0.05). Histological analysis of epididymal white adipose tissue showed naringenin supplementation reduced adipocyte size and number. Between 6 and 8 weeks of diet, mice were assessed in metabolic cages. Naringenin supplementation had no effect on food intake, ambulatory activity or energy expenditure during both the light and dark cycles. Consistently, naringenin-treated mice had significantly lower RER compared to mice fed chow alone (0.97 vs 0.99; P <0.05). This difference was driven by a significant suppression in RER during the light cycle (0.96 vs 1.00; P <0.05), but not the dark cycle (0.97 vs 0.98 N.S ), suggesting an enhanced starvation response. Triglyceride lipolysis was highest in white adipose tissue, followed by liver and muscle. Naringenin supplementation to chow increased the lipolytic rate in adipose, but not in muscle or liver, suggesting reduced adiposity was related to increased expression of ATGL or HSL. In conclusion, compared to chow alone, naringenin supplementation reduced plasma lipids and decreased body weight via increased adipose tissue lipolysis and suppressed RER, with no change in energy expenditure.

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O-093 Energy Expenditure In White Adipose Tissue Is Activated In Response To Brain Tumour Growth

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307384.160 ◽

2014 ◽

Vol 99 (Suppl 2) ◽

pp. A59.3-A60

Author(s):

C Lam ◽

L Robinson ◽

ME Symonds ◽

B Coyle

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

Brain Tumour ◽

White Adipose Tissue ◽

Tumour Growth

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Cocoa powder, cocoa extract and epicatechin attenuate hypercaloric diet-induced obesity through enhanced β-oxidation and energy expenditure in white adipose tissue

Journal of Functional Foods ◽

10.1016/j.jff.2015.10.016 ◽

2016 ◽

Vol 20 ◽

pp. 54-67 ◽

Cited By ~ 20

Author(s):

Griselda Rabadan-Chávez ◽

Lucia Quevedo-Corona ◽

Angel Miliar Garcia ◽

Elba Reyes-Maldonado ◽

María Eugenia Jaramillo-Flores

Keyword(s):

Adipose Tissue ◽

Energy Expenditure ◽

White Adipose Tissue ◽

Cocoa Powder ◽

Diet Induced Obesity ◽

Hypercaloric Diet

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White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00036.2005 ◽

2005 ◽

Vol 289 (2) ◽

pp. R514-R520 ◽

Cited By ~ 40

Author(s):

Haifei Shi ◽

Timothy J. Bartness

Keyword(s):

Adipose Tissue ◽

Body Fat ◽

White Adipose Tissue ◽

Sensory Nerve ◽

Sensory Innervation ◽

Siberian Hamsters ◽

Total Body Fat ◽

Total Body ◽

Lipid Stores ◽

The Brain

The sensory innervation of white adipose tissue (WAT) is indicated by the labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in WAT pads also supports the notion of WAT sensory innervation. The function of this sensory innervation is unknown but could involve conveying the degree of adiposity to the brain. In tests of total body fat regulation, partial surgical lipectomy triggers compensatory increases in the mass of nonexcised WAT, ultimately resulting in restoration of total body fat levels in Siberian hamsters and other animals. The signal that triggers this compensation is unknown but could involve disruption of WAT sensory innervation that accompanies lipectomy. Therefore, a local and selective sensory denervation was accomplished by microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections. Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As seen previously, EWATx resulted in significantly increased retroperitoneal WAT (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen after lipectomy. Collectively, these data suggest the possibility that information related to peripheral lipid stores may be conveyed to the brain via the sensory innervation of WAT.

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Glucose oxidation in white adipose tissue from BIO 14.6 dystrophic hamsters

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-223 ◽

1986 ◽

Vol 64 (10) ◽

pp. 1321-1324

Author(s):

J. Elbrink ◽

E. G. Hunter

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Pentose Phosphate Pathway ◽

Glucose Oxidation ◽

Pentose Phosphate ◽

Muscle Degeneration ◽

Functional Integrity ◽

Enhanced Activity ◽

Retroperitoneal Adipose Tissue

In studies of glucose oxidation in white retroperitoneal adipose tissue of BIO 14.6 dystrophic and FIB normal hamsters aged 55–67 and 368–379 days, no difference was found in the basal state of radiolabelled 14CO2 production using either D-[6-14C]glucose or D-[1-14C]glucose. When C6-labelled glucose was used, insulin induced a slightly greater increase in glucose oxidation in dystrophic adipose tissue at both ages. When C1-labelled glucose was used, insulin enhanced glucose oxidation in dystrophic tissue more than twice normal in tissues from young animals and five times normal in tissues from the old ones. The increase in oxidation with D-[1-14C]glucose likely represents enhanced activity of the pentose phosphate pathway, which has also been observed in certain tissues of other animals with inherited skeletal-muscle degeneration. The change can probably be classified as being compensatory, an attempt by tissues to maintain functional integrity.

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Improved metabolic regulation is associated with retinoblastoma protein gene haploinsufficiency in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00308.2014 ◽

2015 ◽

Vol 308 (2) ◽

pp. E172-E183 ◽

Cited By ~ 12

Author(s):

Petar D. Petrov ◽

Joan Ribot ◽

Andreu Palou ◽

M. Luisa Bonet

Keyword(s):

Adipose Tissue ◽

Body Fat ◽

White Adipose Tissue ◽

Metabolic Regulation ◽

Retinoblastoma Protein ◽

Acid Oxidation ◽

Mature Adult ◽

Adult Age ◽

Enhanced Sensitivity ◽

Partial Deficiency

Retinoblastoma protein (pRb) is involved in the control of energy metabolism, and its inactivation protects mice against high-fat diet-induced diabesity. Here, we tested the hypothesis that partial deficiency in the Rb gene could confer metabolic advantages in front of acute challenges to metabolism and as mice age on a regular diet. Rb haploinsufficient (Rb+/−) mice and wild-type (WT) littermates were studied from weaning and characterized at 1.5–2.5 mo of age (young adults) and 6–7.5 mo of age (mature adults). Whereas no differences in body weight or composition were observed at young age, mature adult Rb+/− mice were leaner than WT littermates, displaying 36% reduced body fat content. At both ages studied, Rb+/− mice displayed improved blood lipids, enhanced sensitivity to the blood glucose-lowering effect of insulin and to the anorectic effect of leptin, and a reduced respiratory exchange ratio, indicative of an increased use of fatty acids as a fuel. Insulin sensitivity and oral fat tolerance were better maintained with age in the Rb+/− than the WT mice. Mature adult Rb+/− mice displayed gene expression changes consistent with increased fatty acid oxidation in white adipose tissue and skeletal muscle and paramount signs of browning in the inguinal white adipose tissue. In conclusion, Rb haploinsufficiency provides metabolic advantages in front of acute metabolic stressors and ameliorates body fat gain and metabolic impairments that normally accompany transition from young to mature adult age.

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Metabolic consequences of hyperinsulinaemia imposed on normal rats on glucose handling by white adipose tissue, muscles and liver

Biochemical Journal ◽

10.1042/bj2670099 ◽

1990 ◽

Vol 267 (1) ◽

pp. 99-103 ◽

Cited By ~ 55

Author(s):

I Cusin ◽

J Terrettaz ◽

F Rohner-Jeanrenaud ◽

B Jeanrenaud

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Glucose Utilization ◽

Insulin Treatment ◽

Driving Forces ◽

Hepatic Glucose Production ◽

Lipid Synthesis ◽

Liver Fat ◽

Insulin Responsiveness

The effects of hyperinsulinaemia imposed on normal rats on the subsequent insulin-responsiveness in vivo of 2-deoxy-D-glucose uptake of white adipose tissue and of various muscle types were investigated. This was done by treating normal rats with insulin via osmotic minipumps, and by comparing them with saline-infused controls. Hyperinsulinaemia produced by prior insulin treatment resulted in a well-tolerated hypoglycaemia. At the end of the treatment, the glucose utilization index of individual tissues was determined by euglycaemic/hyperinsulinaemic clamps associated with the labelled 2-deoxy-D-glucose method. Prior insulin treatment resulted in increased insulin-responsiveness of the glucose utilization index of white adipose tissue, and in increased total lipogenesis in white adipose tissue and fat-pad weight. In contrast, prior insulin treatment resulted in a decreased glucose utilization index of several muscles. These opposite effects of hyperinsulinaemia on glucose utilization in white adipose tissue and muscles persisted when the hypoglycaemia-induced catecholamine output was prevented (adrenomedullectomy, propranolol treatment), as well as when hypoglycaemia was normalized by concomitant insulin treatment and glucose infusion. Insulin suppressed hepatic glucose production during the clamps in insulin-treated rats as in the respective controls, whereas total hepatic lipid synthesis and liver fat content were greater in rats treated with insulin than in controls. It is concluded that hyperinsulinaemia itself could be one of the driving forces responsible for producing increased glucose utilization by white adipose tissue, increased total lipid synthesis with fat accumulation in adipose tissue and the liver, together with an insulin-resistant state at the muscular level.

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Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1519358112 ◽

2015 ◽

Vol 112 (45) ◽

pp. 14006-14011 ◽

Cited By ~ 22

Author(s):

Yifei Miao ◽

Wanfu Wu ◽

Yubing Dai ◽

Laure Maneix ◽

Bo Huang ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Energy Expenditure ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Thyroid Stimulating Hormone ◽

Vital Role ◽

Normal Diet ◽

Subcutaneous White Adipose Tissue ◽

Brown Adipose

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

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