Abstract
Background: Obesity due to an excessive intake of nutrient disturbs the hypothalamus-mediated energy metabolism subsequently develops metabolic disorders. In this study, we investigated the effect of pine needle extract (PNE) on the hypothalamic proopiomelanocortin (POMC) neurons involved in the regulation of energy balance via melanocortin system and fat tissue metabolism. Methods: We performed electrophysiological and immunohistochemical analyses to determine the effect of PNE on POMC neurons. Mice were fed a normal or high-fat diet for 12 weeks, then received PNE for the last 2 weeks to measure the following physiological indices: Body weight, food intake, fat/lean mass, glucose metabolism, and plasma leptin levels. In addition, changes of thermogenic, lipolytic, and lipogenetic markers were evaluated in brown adipose tissue (BAT) and white adipose tissue (WAT) by western blotting, respectively. Results: PNE increased hypothalamic POMC neuronal activity, and the effect was abolished by blockade of melanocortin 3/4 receptors (MC3/4Rs). PNE decreased body weight, fat mass, plasma leptin levels, and improved glucose metabolism after high-fat-induced obesity. However, PNE did not change the expression of thermogenic markers of the BAT in HFD fed groups, but decreased only the lipogenetic markers of WAT. This study suggests that PNE has a potent anti-obesity effect, inhibiting lipogenesis in WAT, even though HFD-induced leptin resistance-mediated disruption of POMC neuronal activity.
Highlights
Endeavors to overcome obesity and type 2 diabetes have become a global issue, given the billions of people suffering from metabolic and related diseases [1,2]
To determine the role of pine needle extract (PNE) related in the hypothalamic regulation of energy balance, we measured c-fos expression levels in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) by immunostaining of the mouse brain slices
The c-fos expression was significantly increased by single oral gavage administration of PNE (200 mg/kg) in both ARC and PVN after 1 h (Figure 1B–D), but not in the ventromedial hypothalamus
Summary
Endeavors to overcome obesity and type 2 diabetes have become a global issue, given the billions of people suffering from metabolic and related diseases [1,2]. The hypothalamus is a key regulator of energy balance between energy intake and expenditure by integrating circulating hormonal and nutritional signals [4,5,6,7]. In the ARC, two types of primary order neurons—including anorexigenic proopiomelanocortin (POMC) and orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons—reciprocally regulate energy balance by sensing glucose and adiposity signals [5,9,10]. There is some evidence that pine needle extract may be helpful to prevent the onset of metabolic disorders and related conditions such as cardiovascular disease, cancer, diabetes, and hypertension [23]. The role of pine needle extract (PNE) on the regulation of energy balance via the hypothalamus remains unclear. We applied pine needle powder obtained by juicing pine needles and freeze-dried it to investigate whether this crude compound affected hypothalamic POMC neurons involved in the regulation of energy balance
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