Explore studies of liver.
BPC 157 prevented liver necrosis and fatty changes in bile duct ligation, restraint stress, and CCl4 models. Effective orally and intraperitoneally. Outperformed bromocriptine, amantadine, and somatostatin.
Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Rotkvic, I; Turkovic, B; Jagic, V; Mildner, B; Duvnjak, M · Animal Study
Fulminant hepatic failure significantly altered Met-enkephalin, Leu-enkephalin, dynorphin A, and beta-endorphin levels in multiple brain regions and plasma.
Yurdaydin, C; Li, Y; Ha, J H; Jones, E A; Rothman, R; Basile, A S · Animal Study
Multiple gastrointestinal peptide hormone levels were significantly altered during acute hepatic cytonecrosis and returned toward normal during liver regeneration.
Budillon, G; Cuomo, R; Taccone, W; Panico, G; Pumpo, R; Iaquinto, G; Manzillo, G · Cross Sectional
BPC-157 both prevented (when co-administered) and reversed (when given after damage) chronic alcohol-induced portal hypertension and liver lesions in rats, measured by direct portal vein pressure and histological assessment.
Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N · Animal Study
GHRP-2 administration prevented endotoxin-induced liver inflammation in rats: reduced hepatic TNF-α, IL-1β, IL-6, and NF-κB activation — demonstrating direct anti-inflammatory hepatoprotection by GH secretagogues independent of GH release.
Granado, Miriam; Martín, Ana Isabel; López-Menduiña, María; López-Calderón, Asunción; Villanúa, M Angeles · Animal Study
AWRK6 (novel GLP-1R agonist from frog AMP) alleviated obesity and hepatic steatosis in HED-induced MAFLD mice, improved lipid and glucose metabolism, and activated PI3K/AKT/AMPK/ACC signaling. Confirmed in human HepG2 fatty liver cell model.
Jin, Lili; Sun, Yuxin; Li, Yuying; Zhang, Hanyu; Yu, Wenxue; Li, Yiling; Xin, Yi; Alsareii, Saeed Ali; Wang, Qiuyu; Zhang, Dianbao · Preclinical (Animal + In Vitro)
PPAR agonists work by making cells more sensitive to insulin. Pioglitazone (a PPARγ agonist) and saroglitazar (a PPARα/γ agonist) are recommended by several medical groups for treating fatty liver in diabetes. Newer PPAR drugs like elafibranor and lanifibranor are also showing promise. GLP-1 receptor agonists take a different approach. They produce significant weight loss and may directly reduce liver inflammation and fibrosis (scarring). The review notes that dual-agonists (like tirzepatide targeting GIP/GLP-1) and triple-agonists have produced even more impressive weight loss, which could further benefit the liver. However, direct evidence of liver benefit from these newer multi-agonists is still limited.
Pramanik, Subhodip; Pal, Partha; Ray, Sayantan · Review
The researchers created a microphysiological system (MPS), a tiny interconnected network of human fat cells, liver cells, and inflammatory immune cells (macrophages). When macrophages inflamed the fat cells, the liver cells accumulated fat and stopped responding to insulin properly. This recreated the early stages of metabolic dysfunction-associated steatotic liver disease (MASLD, previously called NAFLD). Semaglutide improved liver cell function in this system. The key discovery: semaglutide acted on the fat cells, not the liver cells. By calming the inflamed fat cells, semaglutide indirectly reduced liver fat accumulation and restored insulin sensitivity throughout the system.
Qi, Lin; Groeger, Marko; Sharma, Aditi; Goswami, Ishan; Chen, Erzhen; Zhong, Fenmiao; Ram, Apsara; Healy, Kevin; Hsiao, Edward C; Willenbring, Holger; Stahl, Andreas · In Vitro
High-fat diet versus control: liver triglycerides increased 82%, steatosis increased 850%, glucose intolerance increased 71%, insulin increased 98%, and insulin resistance increased 68%. Both drug combinations improved all parameters compared to untreated obese mice: - Empagliflozin + linagliptin: glucose intolerance -60%, insulin -61%, insulin resistance -46%, TAG -61%, steatosis -58% - Empagliflozin + dulaglutide: glucose intolerance -71%, insulin -58%, insulin resistance -62%, TAG -61%, steatosis -82% Principal component analysis clearly separated the groups: the GLP-1 combination was furthest from the disease group, while the DPP-4 combination fell between control and the GLP-1 group.
Reis-Barbosa, Pedro H; Mandarim-de-Lacerda, Carlos A · Animal Study
GLP-1 receptor agonists may treat MAFLD through dual action on the gut-liver axis, reducing liver fat and inflammation while potentially improving gut microbiome balance.
Rochoń, Jakub; Kalinowski, Piotr; Szymanek-Majchrzak, Ksenia; Grąt, Michał · Review
Survodutide achieved MASH improvement without fibrosis worsening in 47% (2.4 mg), 62% (4.8 mg), and 43% (6.0 mg) of participants vs 14% on placebo (P<0.001). Liver fat reduction ≥30% occurred in 57-67% of survodutide groups vs 14% placebo. Fibrosis improved by ≥1 stage in 34-36% vs 22% placebo.
Sanyal, Arun J; Bedossa, Pierre; Fraessdorf, Mandy; Neff, Guy W; Lawitz, Eric; Bugianesi, Elisabetta; Anstee, Quentin M; Hussain, Samina Ajaz; Newsome, Philip N; Ratziu, Vlad; Hosseini-Tabatabaei, Azadeh; Schattenberg, Jörn M; Noureddin, Mazen; Alkhouri, Naim; Younes, Ramy · RCT
Switching from dulaglutide to tirzepatide produced average reductions of 1.2% in HbA1c and 3.6 kg in body weight at 6 months. Liver enzymes (AST, ALT, GGT) significantly decreased. HbA1c reduction correlated with higher baseline HbA1c, while weight loss was baseline-independent. Fibrosis-4 index trended toward improvement in those with higher baseline values.
Sawamura, Toshitaka; Mizoguchi, Ren; Ohmori, Ai; Kometani, Mitsuhiro; Yoneda, Takashi; Karashima, Shigehiro · Cohort
GLP-1RAs vs insulin/no GLP-1RA: pooled HR 0.41 (CI 0.28-0.55), with considerable heterogeneity (I²=74%). GLP-1RAs vs metformin: HR 0.99 (not significant). GLP-1RAs vs DPP-4 inhibitors: HR 1.05 (not significant). GLP-1RAs vs sulfonylureas: HR 0.78 (CI 0.65-0.93).
Shabil, Muhammed; Khatib, Mahalaqua Nazli; Ballal, Suhas; Bansal, Pooja; Tomar, Balvir S; Ashraf, Ayash; Kumar, M Ravi; Sinha, Aashna; Rawat, Pramod; Gaidhane, Abhay M; Sah, Sanjit; Daniel, Afukonyo Shidoiku; Yappalparvi, Ambanna; Bushi, Ganesh · Meta Analysis
Fatty pancreas may be linked to increased risk of pancreatic ductal adenocarcinoma through chronic inflammation and lipotoxicity, and certain diabetes drugs might help.
Otsuka, Nao; Shimamatsu, Yutaka; Hakuta, Ryunosuke; Takayama, Yukiko; Nakai, Yousuke · Narrative Review