iBAT sympathetic innervation is not required for body weight loss induced by central leptin delivery

Côté, Isabelle; Sakarya, Yasemin; Green, Sara M.; Morgan, Drake; Carter, Christy S.; Tümer, Nihal; Scarpace, Philip J.

doi:10.1152/ajpendo.00219.2017

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…The circadian increase in core body temperature during cold exposure was also observed in ob/ob mice treated with LEP (Kaiyala, Ogimoto, Nelson, Muta & Morton 2016). This effect was not dependent on the sympathetic activation of uncoupling protein 1 (UCP1) thermogenesis in the BAT depots, because the denervation of BAT does not prevent weight loss induced by LEP (Cote, Sakarya, Green, Morgan, Carter, Tumer & Scarpace 2018). Although the mechanism for these LEP effects has not been fully elucidated, two hypotheses, based on the humoral (Ukropec, Anunciado, Ravussin & Kozak 2006) and neuroregulatory role (Niijima 1998) of LEP, have been proposed for the control of thermogenesis and lipolysis in a fat depot-specific manner (Niijima 1998).…”

Section: Discussionmentioning

confidence: 99%

Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice

Yasmeen

Shen

Lee

et al. 2018

Journal of Endocrinology

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Adipokine leptin regulates neuroendocrine circuits that control energy expenditure, thermogenesis, and weight loss. However, canonic regulators of leptin secretion, such as insulin and malonyl CoA, do not support these processes. We hypothesize that epiregulin (EREG), a growth factor that is secreted from fibroblasts under thermogenic and cachexia conditions, induces leptin secretion associated with energy dissipation. The effects of EREG on leptin secretion were studied ex vivo, in the intra-abdominal, white adipose tissue (iAb WAT) explants, as well as in vivo, in wild type mice with diet-induced obesity (DIO) and in ob/ob mice. These mice were pair fed a high-fat diet and treated with intraperitoneal injections of EREG. EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway. After 2 weeks, the plasma leptin concentration was increased by 215% in the EREG treated group compared to the control DIO group. EREG treated DIO mice had an increased metabolic rate and core temperature during the active dark cycle, and displayed cold-induced thermogenesis. EREG treatment reduced iAb fat mass, the major site of leptin secretion, but did not reduce the mass of the other fat depots. In the iAb fat, expression of genes supporting mitochondrial oxidation and thermogenesis was increased in EREG-treated mice vs. control DIO mice. All metabolic and gene regulation effects of EREG-treatment were abolished in leptin-deficient ob/ob mice. Our data revealed a new role of EREG in induction of leptin secretion leading to the energy expenditure state. EREG could be a potential target protein to regulate hypo- and hyperleptinemia, underlying metabolic and immune diseases.

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Section: Discussionmentioning

confidence: 99%

Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice

Yasmeen

Shen

Lee

et al. 2018

Journal of Endocrinology

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“…Similarly, in Study 2, leptin transgene expression relative to beta-actin in Leptin treated animals was 5,800-fold that of Control animals ( P < 0.001). Data were reported in previous publications [14,15].…”

Section: Resultsmentioning

confidence: 99%

Oestradiol and leptin have separate but additive anorexigenic effects and differentially target fat mass in rats

Côté

Green

Yarrow

et al. 2018

J Neuroendocrinology

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We recently showed that male compared to female rats exhibit lower hypophagia and body weight (BW) loss following central leptin delivery, suggesting a role for estradiol in leptin responsiveness. Addressing this, we delivered Ob (Leptin) or GFP (Control) gene into the brain of male rats that were simultaneously treated with estradiol or Vehicle. In a reciprocal approach, we compared estradiol-deficient (Ovx) to intact females (Sham) that received Leptin or Control vector. Changes in food intake (FI), BW, and body composition were examined. In males, estradiol and Leptin resulted in lower cumulative food intake (15%) and endpoint body weight (5%) but rats receiving dual treatment (Estradiol-Leptin) ate 28% less and weighed 22% less than Vehicle-Control. Changes in FI were unique to each treatment, with a rapid decrease in Vehicle-Leptin followed by gradual renormalization. In contrast, hypophagia in Estradiol-Control was of lower amplitude and sporadic. Leptin selectively targeted fat mass and endpoint abdominal fat mass was 65–80% lower compared to their respective Control groups. In females, both Leptin groups had lower body weight (endpoint values 20% lower than Control groups) with the highest extent in Sham animals (endpoint value was 28% less in Sham-Leptin than in Sham-Control). Ovx rats rapidly started regaining their lost BW reminiscent of the pattern in males. Leptin rapidly and robustly reduced fat mass with endpoint values 30–35% less than Control treated animals. It appears that Leptin and estradiol decreased FI and BW through different mechanisms, with the pattern of Estradiol-Leptin reminiscent of that observed in females and with the pattern of Ovx-Leptin, reminiscent of that observed in males. Estrogen status did not influence initial fat mass loss by Leptin. It can be concluded that estradiol modulates long-term response to central leptin overexpression but its actions on energy homeostasis are additive and independent of those of leptin.

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“…Leptin, a hormone released by WAT and known for its appetite suppressing effects, was shown to increase SNS activity to BAT (Enriori et al, 2011). However, the IBAT SNS activity was shown to be not necessary for leptin-induced weight loss (Côté et al, 2018). Proopiomelanocortin (POMC) and Agouti-related protein (AgRP) neurons play a role in leptin-mediated increased SNS activity to BAT, while the AgRP are the major regulators of increased SNS activity to the inguinal fat in response to leptin in mice (Bell et al, 2018).…”

Section: Circulating Modulators Of Brown Adipose Activity and Browningmentioning

confidence: 99%

Brown and Brite: The Fat Soldiers in the Anti-obesity Fight

Srivastava

Veech

2019

Front. Physiol.

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Brown adipose tissue (BAT) is proposed to maintain thermal homeostasis through dissipation of chemical energy as heat by the uncoupling proteins (UCPs) present in their mitochondria. The recent demonstration of the presence of BAT in humans has invigorated research in this area. The research has provided many new insights into the biology and functioning of this tissue and the biological implications of its altered activities. Another finding of interest is browning of white adipose tissue (WAT) resulting in what is known as beige/brite cells, which have increased mitochondrial proteins and UCPs. In general, it has been observed that the activation of BAT is associated with various physiological improvements such as a reduction in blood glucose levels increased resting energy expenditure and reduced weight. Given the similar physiological functions of BAT and beige/ brite cells and the higher mass of WAT compared to BAT, it is likely that increasing the brite/beige cells in WATs may also lead to greater metabolic benefits. However, development of treatments targeting brown fat or WAT browning would require not only a substantial understanding of the biology of these tissues but also the effect of altering their activity levels on whole body metabolism and physiology. In this review, we present evidence from recent literature on the substrates utilized by BAT, regulation of BAT activity and browning by circulating molecules. We also present dietary and pharmacological activators of brown and beige/brite adipose tissue and the effect of physical exercise on BAT activity and browning.

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iBAT sympathetic innervation is not required for body weight loss induced by central leptin delivery

Cited by 4 publications

References 39 publications

Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice

Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice

Oestradiol and leptin have separate but additive anorexigenic effects and differentially target fat mass in rats

Brown and Brite: The Fat Soldiers in the Anti-obesity Fight

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