Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells, but Not in Diet-Induced Obese Mice

Abstract

Anthocyanin consumption is linked to benefits in obesity-related metabolic alterations and non-alcoholic fatty liver disease (NAFLD), though the functional role of delphinidin (Dp) is yet to be established. Therefore, this study examined the effects of Dp on metabolic alterations associated with NAFLD, and molecular mechanisms in HepG2 cells and diet-induced obese mice. Cells incubated with palmitate to induce lipid accumulation, concomitantly treated with Dp, reduced triglyceride accumulation by ~53%, and downregulated gene expression of CPT1A, SREBF1, and FASN without modifying AMP-activated protein kinase (AMPK) levels. C57BL/6Nhsd mice were fed a standard diet (control) or a high-fat/high-carbohydrate diet (HFHC) for 16 weeks. Mice in the HFHC group were subdivided and treated with Dp (HFHC-Dp, 15 mg/kg body weight/day) or a vehicle for four weeks. Dp did not affect body weight, energy intake, hyperglycemia, insulin resistance, or histological abnormalities elicited by the HFHC diet. Furthermore, the messenger RNA (mRNA) expressions of Acaca, and Fasn in hepatic or epididymal adipose tissue, and the hepatic sirtuin 1 (SIRT1)/liver kinase B1 (LKB1)/AMPK and proliferator-activated receptor alpha (PPARα) signaling axis did not significantly change due to the HFHC diet or Dp. In summary, Dp effectively reduced triglyceride accumulation in vitro through the modulation of lipid metabolic gene expression. However, a dose of Dp administrated in mice simulating the total daily anthocyanin intake in humans had no effect on either metabolic alterations or histological abnormalities associated with HFHC diets.

Tri-Herbal Medicine Divya Sarva-Kalp-Kwath (Livogrit) Regulates Fatty Acid-Induced Steatosis in Human HepG2 Cells through Inhibition of Intracellular Triglycerides and Extracellular Glycerol Levels

“…SKK treatment brought down this upregulated CPT1A levels to the normal level. This apparent normalization of CPT1A levels post SKK treatment points towards a chain of events leading to the attainment of homeostasis by the cells [ 58 , 59 ]. Prolonged enhancement of CPT1A activity can lead to increased mitochondrial energy metabolism leading to heightened reactive oxygen species generation and causing cellular damage and apoptosis [ 60 ].…”

“…While in-vitro and ex-vivo models are good for exploring the molecular mechanisms, their results often depict signs of singularity in response. One example can be a study performed by Parra-Vargas et al wherein they found that their test compound delphinidin used for reducing steatosis showed efficacy in vitro but not in their high-fat diet mouse model [ 59 ]. Another likely limitation is the lack of immune profiling, which is involved in the progression to fibrosis.…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…Anthocyanins and anthocyanins-rich foods extracts or juices have demonstrated in several studies their ability to reduce the hepatic content of TG and lipids [ 85 , 86 ] and their capacity to modulate hepatic metabolism to protect against NAFLD [ 62 , 87 , 88 , 89 ]. Although in most of the published approaches performed with rodent models of obesity or NAFLD, anthocyanins or anthocyanin-rich fruits or extracts significatively reduced the hepatic lipid content and ameliorated the hepatic steatosis profile of these animals [ 88 , 90 , 91 , 92 ] some ineffective approaches have also been described [ 93 , 94 , 95 ].…”

Select Polyphenol-Rich Berry Consumption to Defer or Deter Diabetes and Diabetes-Related Complications

“…LPS treatment increased IL-6, MCP-1, TNF-α, and galectin-3 with decreased adiponectin expression, which was countered and reversed by MqBEs in macrophages [ 220 ]. Furthermore, a dose of 100 and 180 µM MqB delphinidin inhibited sodium palmitate-induced-TG-accumulation by 50 and 59%, respectively, in Hep2G cells [ 222 ].…”

“…Delphinidin supplementation limited weight gain in HFD-fed C57BL/6Nhsd mice, but not increased liver weight. Glucose homeostasis variations induced by HFD/HCD were also minimized by delphinidin treatment [ 222 ]. Hidalgo et al [ 327 ] showed that delphinidin supplementation in rat jejunum tissues/cells reduced the short circuit current generated by glucose addition to an Ussing chamber.…”