Spilanthol from Traditionally Used Spilanthes acmella Enhances AMPK and Ameliorates Obesity in Mice Fed High-Fat Diet

Abstract

Spilanthol (SP) is a bioactive compound found in Spilanthes acmella, giving the flowers and leaves a spicy taste. Studies found that phyto-ingredients stored in spice plants act against obesity-related diseases. SP has antimicrobial, anti-inflammatory, and analgesic properties, but the effects on obesity are not yet known. We investigated the effects of SP in differentiated adipocytes (3T3-L1 cells) and mice fed a high-fat diet (HFD). SP significantly inhibited intracellular lipid accumulation and significantly reduced the expression of lipogenesis-related proteins, including acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FAS). In contrast, SP increased the expression of carnitine palmitoyltransferase (CPT)1 and AMP-activated protein kinase (AMPK) in adipocytes. However, SP suppressed the levels of cyclooxygenase-2 (COX-2), phospho-p38 (pp38), and phospho-JNK (c‑Jun N-terminal kinase) (pJNK) in LPS (lipopolysaccharide)-stimulated murine pre-adipocytes. SP administered to HFD-induced obese mice via intraperitoneal injections twice a week for 10 weeks decreased body weight gain, visceral adipose tissue weight, and adipocyte size. SP inhibited lipogenic proteins FAS and ACC, and suppressed adipogenic transcription factors, enhancing lipolysis and AMPK protein expression in the liver. SP has anti-obesity effects, upregulating AMPK to attenuate lipogenic and adipogenic transcription factors.

Nifedipine Exacerbates Lipogenesis in the Kidney via KIM-1, CD36, and SREBP Upregulation: Implications from an Animal Model for Human Study

“…The results of the current study are also consistent with those of our previous in-vitro study [ 18 ], in which NF was found to activate SREBP-1/2 and suppress AMPK, leading to lipogenesis and lipid accumulation. An interesting study using HFD mice showed that upregulated AMPK inhibited lipogenic and adipogenic transcriptional factors [ 22 ]. Furthermore, a high-energy status, such as that occurring in obesity, and calcium channel blockers, such as NF, may induce a low active form of AMPK (p-AMPK), thereby reducing energy production.…”

Potential Antioxidant and Anti-Inflammatory Effects of Spilanthes acmella and Its Health Beneficial Effects: A Review

“…These actions were enough to block allergic inflammation. Spilanthol (3 µM to 100 µM) was also found to reduce inflammatory response by downregulating MAPK signaling pathways in 3T3-L1 pre-adipocytes [ 69 ]. Literature shows that obesity-induced chronic low-grade inflammation could lead to the development of various metabolic diseases.…”

“…Huang et al [ 69 ] demonstrated that spilanthol (5 mg/kg and 10 mg/kg) might help in preventing pre-adipocyte inflammatory responses to reduce obesity-related metabolic diseases. Spilanthol significantly suppressed inflammatory mediator COX-2, promoted anti-inflammatory protein heme oxygenase-1 (HO-1) expression, and blocked the phosphorylation of c-Jun N-terminal kinase (JNK), as well as P38 protein in LPS-stimulated murine pre-adipocytes.…”

Liraglutide may affect visceral fat accumulation in diabetic rats via changes in FTO, AMPK, and AKT expression

“…Similarly, a polymorphism at FTO rs9939609 is significantly associated with hyperlipidemia, obesity, and insulin metabolism, and this association is mediated by target tissue receptors. Moreover, activation of the SIRT-AMPK signaling pathway reduces the expression of fatty acid synthases and associated transcription factors, increases the oxidation rate of fatty acids, and regulates lipid and energy metabolism [17][18][19].…”