Gelidium elegans Regulates the AMPK-PRDM16-UCP-1 Pathway and Has a Synergistic Effect with Orlistat on Obesity-Associated Features in Mice Fed a High-Fat Diet

Abstract

The incidence of obesity is rising at an alarming rate throughout the world and is becoming a major public health concern with incalculable social and economic costs. Gelidium elegans (GENS), also previously known as Gelidium amansii, has been shown to exhibit anti-obesity effects. Nevertheless, the mechanism by which GENS is able to do this remains unclear. In the present study, our results showed that GENS prevents high-fat diet (HFD)-induced weight gain through modulation of the adenosine monophosphate-activated protein kinase (AMPK)-PR domain-containing16 (PRDM16)-uncoupling protein-1 (UCP-1) pathway in a mice model. We also found that GENS decreased hyperglycemia in mice that had been fed a HFD compared to corresponding controls. We also assessed the beneficial effect of the combined treatment with GENS and orlistat (a Food and Drug Administration-approved obesity drug) on obesity characteristics in HFD-fed mice. We found that in HFD-fed mice, the combination of GENS and orlistat is associated with more significant weight loss than orlistat treatment alone. Moreover, our results demonstrated a positive synergistic effect of GENS and orlistat on hyperglycemia and plasma triglyceride level in these animals. Thus, we suggest that a combination therapy of GENS and orlistat may positively influence obesity-related health outcomes in a diet-induced obese population.

Antiadipogenic effects of a standardized quassinoids‐enriched fraction and eurycomanone from Eurycoma longifolia

“…In this regard, Gao et al, () have successfully demonstrated the reduction of body weight gain in mice was mediated by an increase in energy expenditure and fatty acid oxidation through the actions of PGC‐1α and UCP‐1 in their study on butyrate supplementation. In addition, other studies have demonstrated the involvement of the adenosine monophosphate‐activated protein kinase (AMPK)‐PR domain‐containing16 (PRDM16)‐uncoupling protein‐1 (UCP‐1) pathway in increased calorie expenditure in mice models (Choi, Kim, Koh, & Lee, ; Kudo et al, ). AMPK regulates energy metabolism by stimulating the interaction between PGC1α and PRDM16 resulting in increased mitochondrial biogenesis, thermogenesis, and energy expenditure (Zhang et al, ).…”

“…PGC-1α is known to stimulate adaptive thermogenesis in brown fat by upregulating uncoupling protein 1 (UCP-1), which in turn increases oxidative type 1 fiber differentiation and enhances fatty acid metabolism in the muscle. In this regard, Gao et al, (2009) (UCP-1) pathway in increased calorie expenditure in mice models (Choi, Kim, Koh, & Lee, 2017;Kudo et al, 2015). AMPK regulates energy metabolism by stimulating the interaction between PGC1α and PRDM16 resulting in increased mitochondrial biogenesis, thermogenesis, and energy expenditure .…”

Gelidium elegans Extract Ameliorates Type 2 Diabetes via Regulation of MAPK and PI3K/Akt Signaling

“…One example of note is Gelidium elegans extract (GEE), previously known as Gelidium amansii , an edible seaweed native to the Asia Pacific region [ 31 ]. We have described the bioactivity of GEE, including its anti-oxidant, anti-hyperglycemic, and anti-obesity effects [ 32 , 33 , 34 ]. Our previous study showed that GEE has the potential to regulate energy metabolism in high fat diet-induced obese mice [ 32 ], and in particular it may regulate glucose homeostasis [ 35 ].…”

Curcumin Activates AMPK Pathway and Regulates Lipid Metabolism in Rats Following Prolonged Clozapine Exposure

“…AMP-activated protein kinase (AMPK) has emerged as a key regulator in hepatic energy metabolism and lipid homeostasis. Activation of AMPK suppresses fatty acid and cholesterol biosynthesis, by inhibiting the activity of acetyl CoA carboxylase (ACC) and 3-hydroxy-3-methyl glutaryl CoA reductase (HMGR; Li et al, 2014 ; Choi et al, 2017 ). In addition, AMPK can inactivate sterol regulatory element-binding proteins (SREBPs), the major transcriptional regulators of lipogenesis, and thereby inhibit the downstream lipogenic genes (Jang et al, 2017 ).…”