Table 2.

Mechanisms of action of antiobesity peptides derived from various food sources.

Dietary protein source	Enzyme used to produce peptides	Peptide sequence or molecular weight	Object	Dose & duration	Activity/mechanisms of action	Reference
Soy protein	Flavourzyme	<1300 Da	3T3-L1 preadipocytes	100 ppm for 8 d	Peptides reduced GPDH activity and inhibited adipogenesis by affecting the expression of PPAR-γ and CCAAT/enhancer binding protein-α	[123]
Smooth hound (Mustelus mustelus) muscle protein	Alkaline crude enzymes from M. mustelus intestines	200–2500 Da	Rats	0.5 mL (10 mg/mL)/day/kg BW for 21 d	Peptides reduced BW and food intake	[5]
Soy protein	Flavourzyme	ILL, LLL, and VHVV	3T3-L1 adipocytes	4 ppm for 72 h	Peptides exhibited lipolysis-stimulating activity	[52]
Canola protein	Alcalase, chymotrypsin, pepsin trypsin, and pancreatin	<1–10 kDa	C3H10T1/2 murine mesenchymal stem cells	60–100 μg/mL for 24 h	Peptides showed antiobesity effects by inhibiting PPARγ expression and pancreatic lipase	[54]
Common bean	Alcalase, bromelain, and pepsin-pancreatin	<1 kDa	Mature adipocytes 3T3-L1	0.1, 1, 10, and 100 μg/mL for 48 h	Peptides inhibited lipid accumulation (28%)	[53]
Salmon protein	—	—	Placebo-controlled, randomized clinical study	16 g for 42 days	Peptide supplementation for 42 days reduced the body mass index by 5.6% in overweight subjects	[59]
Ark shell (Scapharca subcrenata) protein	Pepsin	<1 kDa	Mouse mesenchymal stem cells	400 μg/mL for 7 d	Peptides inhibited intracellular lipid accumulation and enhanced lipolysis. Peptides inhibited adipogenesis by downregulating the adipocyte-specific protein expression including PPAR-γ, C/EBP-α, SREBP-1c, downstream lipoprotein lipase, and FAS expression	[51]
Yellow catfish protein	Alcalase	—	HFD fed mice	500, 250 and 125 mg/kg BW for 84 d	Peptides exhibited anti-obesity effects	[124]
Sardinella (Sardinella aurita) protein	Bacillus subtilis A26 and Bacillus amyloliquefaciens An6	150–900 Da	Wistar rats fed high caloric diet	400 mg/kg BW for 10 weeks	Peptides reduced BW gain, food intake, and the relative epididymal adipose tissue and decreased the pancreatic lipase activity	[2]
Alaska pollack protein	Pepsin and pancreatin	—	Rats	0, 100, and 300 mg/kg BW for 3 d	Peptides reduced white adipose tissue weight and food intake	[56]
Tuna skin	Subcritical water hydrolysis	—	3T3-L1 preadipocytes and obese mice fed HFD	300 mg/kg/day for 8 weeks	Peptides decreased HFD-induced BW gain and inhibited the expression of C/EBP-α, PPAR-γ and adipocyte protein 2	[55]
Camel whey protein	Pepsin, trypsin, and chymotrypsin	<10 kDa	In vitro assays	50 μL for 30 min	Peptides exhibited antiobesity effects by inhibiting pancreatic lipase and cholesteryl esterase enzymes	[125]
Skate (Raja kenojei) skin collagen	—	1050 Da	HFD-fed mice	100, 200, or 300 mg/kg BW for 8 weeks	Peptides showed antiobesity effects by reducing BW gain and visceral adipose tissue and improved the dyslipidemia via regulating hepatic lipid metabolism and AMPK	[126]
Camel milk	Alcalase, bromelin, and papain	<10 kDa	In vitro	—	Peptides inhibited the porcine pancreatic lipase	[24]
Kefir	—	>30 kDa, 3–30 kDa, and <3 kDa	HFD-induced obese rats	164 mg/kg BW daily for 8 weeks	Peptides blocked lipogenesis by reducing FAS and increased p-acetyl-CoA carboxylase. Peptides enhanced FA oxidation via increasing the expressions of phosphorylated AMPK, PPAR-α, and hepatic carnitine palmitoyltransferase-1	[127]
Spirulina platensis protein	Trypsin, alcalase, pepsin, papain, and protamex	NALKCCHSCPA, LNNPSVCDCDCMMKAAR, NPVWKRK, and CANPHELPNK	3T3-L1 preadipocytes	1 mg/mL for 48 h	Peptides exhibited antiobesity effects by inhibiting lipase (72%) and 3T3-L1 preadipocytes (72.7–88.1%) and decreased triglyceride accumulation	[8]
Quinoa protein	Papain, pepsin, and pancreatin	FGVSEDIAEKLQAKQDERGNIVL, AEGGLTEVWDTQDQQF, YIEQGNGISGLMIPG, AVVKQAGEEGFEW, and HGSDGNVF	3T3-L1 cells	0–1600 μg/mL for 48 h	Peptides inhibited lipid accumulation during differentiation and suppressed cell differentiation through PPAR-γ	[128]
Spirulina platensis protein	Pepsin	<10 kDa	HFD-fed mice	2 g/kg BW/d for 4 weeks	Peptides showed antiobesity effects reducing BW, lowering serum glucose, and total cholesterol through modulation of expressions of Acadm, Retn, Fabp4, Ppard, and Slc27a1 in the brain and liver	[57]
Pea (Pisum sativum L.) seed proteins	Pepsin and pancreatin	<6 kDa	3T3-L1 murine preadipocytes	0, 1, 2, 4, and 6 mg/mL for 24 h	Peptides stimulated adipocyte differentiation through upregulation of PPAR-γ expression and ligand activity	[48]
Walleye pollock skin collagen	Flavourzyme and alcalase	500–5000 Da	HFD-fed C57BL/6J mice	800 mg/kg BW for 8 weeks	Peptides inhibited weight gain, adipocyte growth, adipose tissue accumulation, and liver weight and reduced the blood-lipid level	[58]
Blue mussel	Pepsin	<1 kDa	Mouse mesenchymal stem cells	100, 200, and 400 μg/mL for 7 or 21 d	Peptides enhanced lipolysis and downregulated adipogenic transcription factors including PPARγ, CCAAT/enhancer-binding protein-α, and SREBP-1	[10]
Hazelnut (Corylus heterophylla Fisch) protein	Alcalase	Arg-Leu-Leu-Pro-His	3T3-L1 adipocytes	0, 20, 40, and 80 mM for 8 d	Peptides decreased adipogenesis by downregulating the expression of PPAR-γ, C/EBP-α, aP2, SREBP-1c, FAS, ACC1, and 3-hydroxy-3-methylglutaryl-CoA reductase	[13]
Milk β-casein	Trypsin	7 kDa	HepG2 cells and humans	5 mg/mL for 24 h	Casein oligopeptide increased FGF-21	[129]

ACC1: acetyl-CoA carboxylase 1; AMPK: AMP-activated protein kinase; aP2: adipocyte fatty acid-binding protein 2; BW: body weight; C/EBP-α: CCAAT/enhancer binding protein alpha; FAS: fatty acid synthase; FGFs: fibroblast growth factors; HFD: high-fat diet; PPAR-γ: peroxisome proliferator-activated receptor-γ; SREBP-1: sterol regulatory element-binding protein 1.