Stearoyl CoA desaturase 1 (SCD1) is a central regulator of fuel metabolism and may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets. In this review, we evaluate the role of SCD1 isoform in regulation of lipid and glucose metabolism in metabolic tissues. These highlights of recent findings are aimed towards advancing our understanding of the role of SCD1 in the development of metabolic diseases which may help evaluate the possible health outcomes of modulating MUFA levels through targeting SCD1 activity.

Stearoyl CoA desaturase 1 (SCD1) is a key enzyme in lipogenesis as it catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate (18:1n9) and palmitoleate (16:1n7) from saturated fatty acids (SFA), stearate (18:0) and palmitate (16:0), respectively. Studies on SCD1 deficiency in mouse models demonstrated beneficial metabolic phenotypes such as reduced adiposity and improved glucose tolerance. Even though, SCD1 represents a potential target to resolve obesity related metabolic diseases; SCD1 deficiency causes endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR). The induction of ER stress in response to SCD1 deficiency is governed by the cofactor, PGC-1α. However, the mechanism by which SCD1 deficiency increases PGC-1α and subsequently induces ER stress still remains elusive. The present study demonstrates that despite reduced lipogenesis, liver specific SCD1 deficiency activates the mechanistic target of rapamycin complex 1 (mTORC1) along with induction of PGC-1α and ER stress. Further, mTORC1 inhibition attenuates SCD1 deficiency-mediated induction of both PGC-1α and ER stress. Similar observations were seen by restoring endogenously synthesized oleate, but not palmitoleate, suggesting a clear mTORC1-mediated regulation of ER stress during SCD1 deficiency. Overall, our results suggest a model whereby maintaining adequate levels of hepatic oleate is required to suppress mTORC1-mediated ER stress. In addition, the activation of mTORC1 by SCD1 deficiency reveals an important function of fatty acids in regulating different cellular processes through mTORC1 signaling.

Increased carbohydrate consumption increases hepatic de novo lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids, oleate and palmitoleate, from the saturated fatty acids stearate and palmitate, respectively. SCD1deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia. However, the mechanism of this protection by SCD1 deficiency is unclear. Using liver-specific SCD1 knockout (LKO) mice fed a high-carbohydrate, low-fat diet, we show that hepatic SCD1 deficiency increases systemic glucose uptake. Hepatic SCD1 deficiency enhanced glucose transporter type 1 (GLUT1) expression in the liver and also up-regulated GLUT4 and adiponectin expression in adipose tissue. The enhanced glucose uptake correlated with increased liver expression and elevated plasma levels of fibroblast growth factor 21 (FGF21), a hepatokine known to increase systemic insulin sensitivity and regulate whole-body lipid metabolism. Feeding LKO mice a triolein-supplemented but not tristearin-supplemented high-carbohydrate, low-fat diet reduced FGF21 expression and plasma levels. Consistently, SCD1 inhibition in primary hepatocytes induced FGF21 expression, which was repressed by treatment with oleate but not palmitoleate. Moreover, deletion of the transcriptional coactivator PPAR␥ coactivator 1␣ (PGC-1␣) reduced hepatic and plasma FGF21 and white adipocyte tissue-specific GLUT4 expression and raised plasma glucose levels in LKO mice. These results suggest that hepatic oleate regulates glucose uptake in adipose tissue either directly or partially by modulating the hepatic PGC-1␣-FGF21 axis.

Melanoma remains an important health concern, given the steady increase in incidence and acquisition of resistance to systemic therapies. The receptor for advanced glycation end products (RAGE) initially identified for its binding to advanced glycation end products was subsequently acknowledged as a pattern recognition receptor given its ability to recognize similar structural elements within numerous ligands. Recent studies have elucidated a plausible role of RAGE in melanoma progression through modulation of inflammatory, proliferative and invasive cellular responses. Several of its ligands including the S100 proteins and HMGB1 are being investigated for their involvement in melanoma metastasis and as potential biomarkers of the disease. Targeting RAGE signaling represents a viable therapeutic strategy which remains underexplored in cutaneous malignancies. Here we have summarized current knowledge on the functionality of RAGE with special focus on specific ligands enumerated in various in vitro and in vivo melanoma models.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.

Musculoskeletal symptoms related to orthopedic conditions are highly prevalent worldwide and are a leading cause of morbidity. However, non-orthopedic conditions may also present with musculoskeletal symptoms. For example, shoulder pain may be caused by gastrointestinal, hepatobiliary, cardiac, and neurological pathologies. We report the case of a 32-year-old man who presented to the orthopedic clinic with a complaint of left shoulder pain for the past three months. He described the pain as sharp in nature. The pain was constant and was not related to the shoulder movements. It was not associated with morning stiffness. He had no history of preceding trauma. On examination, both shoulders were symmetrical with no evidence of deformities. Palpation over the shoulder region did not elicit any tenderness. The range of motion in both the active and passive movements was intact. The Neer and Jobe tests were negative. Also, the sensory examination was intact, and laboratory findings were normal. The patient underwent a plain frontal radiograph of the chest, which revealed a large well-circumscribed lobulated mass lesion in the left hemithorax, arising from the pleural lining. A thoracic CT scan was then performed to provide further characterization of the mass lesion and it re-demonstrated the mass as having homogeneous fatattenuation with thin septations, probably representing pleural lipoma. The tumor was successfully resected via open thoracotomy. The patient's symptoms resolved and he had no recurrence after one year of followup. Pleural lipoma is a very rare benign mesenchymal tumor. The case highlights the importance of considering non-orthopedic conditions in the differential diagnosis of shoulder pain in patients with normal physical examination findings. A CT scan is vital to make the diagnosis and can show the accurate anatomic relations with respect to the tumor for surgical planning.

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Test smells are defined as sub-optimal design choices developers make when implementing test cases. Hence, similar to code smells, the research community has produced numerous test smell detection tools to investigate the impact of test smells on the quality and maintenance of test suites. However, little is known about the characteristics, type of smells, target language, and availability of these published tools. In this paper, we provide a detailed catalog of all known, peer-reviewed, test smell detection tools.We start with performing a comprehensive search of peer-reviewed scientific publications to construct a catalog of 22 tools. Then, we perform a comparative analysis to identify the smell types detected by each tool and other salient features that include programming language, testing framework support, detection strategy, and adoption, among others. From our findings, we discover tools that detect test smells in Java, Scala, Smalltalk, and C++ test suites, with Java support favored by most tools. These tools are available as command-line and IDE plugins, among others. Our analysis also shows that most tools overlap in detecting specific smell types, such as General Fixture. Further, we encounter four types of techniques these tools utilize to detect smells. We envision our study as a onestop source for researchers and practitioners in determining the tool appropriate for their needs. Our findings also empower the community with information to guide future tool development.