Obesity is a chronic metabolic disease that endangers health worldwide, and features disorders of lipid metabolism and insulin resistance, as well as chronic low-grade inflammation . The high-fat diet is an environmental factor that can cause obesity by the abnormal accumulation of lipids. Lactobacillus is a probiotic with anti-obesity effects, and it may act by regulating the intestinal flora and protecting intestinal mucosa, and modulating lipid and energy metabolism pathways, inflammation, and the oxidative stress state [28–32]. A high-fat diet can significantly increase the weight of mice, but LF-CQPC07 controlled weight gain in mice and the increase in white adipose tissue to achieve the purpose of alleviating obesity.
Excessive lipid accumulation is mainly manifested by increase and hypertrophy of adipocytes [33, 34]. Hypertrophy of adipocytes leads to endocrine dysfunction, in which there is increased secretion of proinflammatory adipokines such as TNF-α, IL-1, IL-6, and chemokines monocyte chemoattractant protein [33, 34]. Obesity is accompanied by excessive ROS, and the body's antioxidant defense capacity is reduced, causing an oxidative stress response . ROS activates the TNF, NF-κB, and JNK signaling pathways to induce apoptosis and inflammation [36, 37]. Therefore, obese people are in a chronic low inflammatory state. In the model group, the adipose tissue of mice was significantly hypertrophic compared with other groups, and serum levels of pro-inflammatory cytokines TNF-α, IL-6, IL-1β, and IFN-γ were increased, while anti-inflammatory factors IL-10 and IL-4 levels were decreased. Tissue sections showed that LF-CQPC07 alleviates the hypertrophy of adipocytes, and it also significantly reduced the levels of the anti-inflammatory factors TNF-α, IL-6, IL-1β, and IFN-γ, and increased the levels of anti-inflammatory factors IL-10, IL-4, thereby inhibiting chronic low-grade inflammation associated with obesity.
Obesity can be complicated with lipid metabolic disorders that are characterized by an increase in TC, TG, and LDL-C and a decrease in HDL-C. It is also the main cause of endovascular disease . In the model group, the high-fat diet significantly increased the levels of TG, TC, and LDL-C, and decreased the level of HDL-C, indicating that mice were in a lipid metabolic disorder. After intragastric administration of LF-CQPC07, it was observed that the HDL-C level increased, and the TC, TG and LDL-C levels decreased. This showed that LF-CQPC07 relieved the disorder of lipid metabolism caused by a high-fat diet.
The liver is an important metabolic organ. Lipid metabolic disorders in the liver result in lipid deposition and fat accumulation, which induces hepatocyte steatosis and increases gluconeogenesis. Subsequently, insulin resistance and oxidative stress develop, and then, ROS-induced hepatocyte inflammation occurs, leading to hepatocyte injury . From the results of the liver tissue sections and ALT, AST, and ALP levels , which are the clinical indicators of liver function, it was revealed that the hepatocytes of mice in the model group were damaged. The experimental results revealed that LF-CQPC07 decreased the levels of ALT, AST, and ALP and significantly relieved hepatocyte injury.
Obese people often undergo oxidative stress, resulting in disorders of energy metabolism, signal transduction, and other cellular functions . The system that defends against oxidative stress is mainly composed of enzymatic and non-enzymatic antioxidants such as CAT, GSH-Px, SOD, and GSH . SOD scavenges superoxide radicals by means of copper, zinc, and manganese ions as auxiliary groups . CAT directly converts hydrogen peroxide into water and oxygen. The reaction of H2O2 and GSH to form H2O and oxidized glutathione (GSSG) is catalyzed by GSH-Px . In the model group, mRNA expression of SOD1, SOD2, CAT, GSH-Px, and GSH1 was significantly suppressed, indicating that the antioxidant capacity of obese mice decreased. LF-CQPC07 upregulated the mRNA expression of SOD1, GSH-Px, SOD2, CAT, and GSH1 to increase the body's antioxidant capacity and inhibit oxidative stress, thereby relieving liver damage and inflammation caused by obesity.
The peroxisome proliferator-activated receptor (PPAR) family is widely recognized as a lipid sensor that is involved in regulating lipids, glucose metabolism, and energy metabolism [42, 43]. The expression of PPAR-α is detected in many tissues, but its highest expression occurs in the liver. It is critical in regulating fatty acid uptake, β-oxidation of fatty acids, ketogenic effects, bile acid synthesis, and triglyceride conversion , and PPAR-α signaling inhibits lipid accumulation and subsequent oxidative stress. PPAR-γ is another member of the PPAR family that is an essential transcription factor in regulating lipid metabolism [45, 46]. It participates in fat metabolism and promotes synthesis, transport, and lipid deposition by regulating the transcription of lipid metabolism-related genes [45, 46]. In addition, PPAR-γ acts as a key factor in early adipocyte differentiation and it promotes the expression of C/EBP-α, and then they work together to induce adipocyte differentiation and lipid deposition [47, 48].
LPL and CPT1, as downstream target genes for PPAR-α and PPAR-γ signaling, directly regulate lipid metabolism [45, 49]. LPL is a key rate-limiting enzyme for hydrolyzing triglycerides, and can remove triglyceride-rich proteins including very low-density lipoprotein (VLDL), LDL, and chylomicron, and increase HDL levels . As the rate-limiting enzyme for the β-oxidation of fatty acid, CPT1 catalyzes the synthesis of fatty acyl carnitine by long-chain fatty acyl CoA and carnitine . CYP7A1 catalyzes cholesterol transformed into cholic acid. It is the rate-limiting enzyme in the classic pathway of bile acid synthesis, and maintains cholesterol homeostasis and bile acid synthesis . LF-CQPC07 upregulates the mRNA expression of PPAR-α, LPL, CPT1, and CYP7A1 and downregulates the mRNA expression of PPAR-γ and C/EBP-α to inhibit the differentiation and proliferation of adipocytes, promote the β-oxidation of fatty acid and decomposition of triglyceride and cholesterol, and reduce the accumulation of lipid, thereby ameliorating the disorder of lipid metabolism and inhibiting obesity.