  Citation: Tsai, S.-C.;Huang, Y.-W.; Wu, C.-C.; Wang, J.-J.; Chen, Y.-T.; Singhania, R.R.; Chen, C.-W.; Dong, C.-D.; Hsieh, S.-L. Anti-Obesity Effect of Nostoc commune Ethanol Extract In Vitro and In Vivo. Nutrients 2022, 14, 968. https://doi.org/10.3390/ nu14050968 Academic Editor: Lindsay Brown Received: 13 January 2022 Accepted: 22 February 2022 Published: 24 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Article Anti-Obesity Effect of Nostoc commune Ethanol Extract In Vitro and In Vivo Sheng-Chieh Tsai 1,2 , Yu-Wen Huang 1 , Chih-Chung Wu 3 , Jyh-Jye Wang 4 , Ya-Ting Chen 1 , Reeta Rani Singhania 5 , Chiu-Wen Chen 5 , Cheng-Di Dong 5 and Shu-Ling Hsieh 1, * 1 Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan; b220682837@gmail.com (S.-C.T.); may2377234@gmail.com (Y.-W.H.); melodyyu.chen@gmail.com (Y.-T.C.) 2 Department of Medical Research, E-Da Hospital, Kaohsiung 82445, Taiwan 3 Department of Food and Nutrition, Providence University, Taichung 43301, Taiwan; wuccmail@gmail.com 4 Department of Nutrition and Health Science, Fooyin University, Kaohsiung 83102, Taiwan; ft054@fy.edu.tw 5 Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 81157, Taiwan; reetasinghania@nkust.edu.tw (R.R.S.); cwchen@nkust.edu.tw (C.-W.C.); cddong@nkust.edu.tw (C.-D.D.) * Correspondence: slhsieh@nkust.edu.tw; Tel.: +886-7-361-7141 (ext. 23626) Abstract: Nostoc commune is an edible terrestrial blue-green alga. It has shown many beneficial effects on human health. This study aimed to investigate the phytochemical assay of N. commune ethanol extract (NEE) and its anti-obesity effects. The effect of a high-calorie diet on lipid accumulation in 3T3-L1 preadipocytes is investigated, and a Wistar rat model is used to demonstrate the anti-obesity effect of NEE and its mechanism. The results showed that the NEE has phytochemical compounds, such as total polyphenol, total flavonoids, and total terpenoids. NEE was also shown to suppress cell proliferation and lipid accumulation (26.9%) in 3T3-L1 preadipocytes. Furthermore, NEE reduced the body weight (13.5%), fat tissue weight (13.3%), and the serum FFA (19.4%), TG (14.2%), TC (11.8%), and LDL-C (16.4%) of rats. In histopathology, NEE was shown to diminish the size of adipocytes and hepatic lipid droplets. The NEE downregulated the mRNA expression of adipogenesis (PPAR-γ, SREBP-1c) and lipid lysis-related genes (ATGL, HSL) in epididymal adipose tissue. The NEE also upregulated the mRNA expression of β-oxidation related genes (AMPK, CPT-1, PPAR-α) in the liver. Overall, this study suggests NEE has the potential to be developed as a functional food for anti-obesity. Keywords: Nostoc commune; phytochemical; anti-oxidations ability; 3T3-L1 pre-adipocytes; obesity 1. Introduction Obesity is defined as an excess of fatty tissue in the body, which increases the risk of a variety of chronic illnesses and body function disorders, such as diabetes mellitus type 2, hypertension, cardiovascular disease, and obese sarcopenia. [1,2]. Adipocyte size and quan- tity increase, resulting in a low-grade pro-inflammatory milieu in adipose tissue, which leads to fat gain [3]. It is important to study the role of fat in obesity for the prevention as well as treatment of obesity. Lipogenesis and lipolysis are important processes for the con- trol of adipocyte energy balance. Peroxisome proliferator-activated receptor γ (PPARγ) is one of the transcription factors that is important in the transformation of preadipocytes into mature adipocytes; sterol regulatory element-binding protein (SREBP) expression helps triglyceride synthesis in adipocytes, which leads to adipocyte lipid accumulation [4,5]. In addition, a decrease in adipocyte size is an effective therapy for obesity. Adenosine monophosphate-activated protein kinase (AMPK) is a key factor of energy homeostasis, because it is a fuel-sensing enzyme that is activated by an increased ratio of AMP/ATP and is sensitive to nutrition conditions [6,7]. Hormone-sensitive lipase (HSL) and adipose Nutrients 2022, 14, 968. https://doi.org/10.3390/nu14050968 https://www.mdpi.com/journal/nutrients