Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice

• Published in: Endocrinology (Philadelphia) Vol. 156; no. 12; pp. 4502 - 4510
• Main Authors: Mastaitis, Jason, Eckersdorff, Mark, Min, Soo, Xin, Yurong, Cavino, Katie, Aglione, Johnpaul, Okamoto, Haruka, Na, Erqian, Stitt, Trevor, Dominguez, Melissa G, Schmahl, Jennifer P, Lin, Calvin, Gale, Nicholas W, Valenzuela, David M, Murphy, Andrew J, Yancopoulos, George D, Gromada, Jesper
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01-12-2015; Oxford University Press
• Subjects: Animals; Beta cells; Blood Glucose - metabolism; Body composition; Body Composition - genetics; Body length; Body mass; Body size; Body Size - genetics; Body weight; Body weight gain; Bone density; Bone Density - genetics; Bone mass; Bone mineral density; Diabetes mellitus (non-insulin dependent); Diet; Diet, High-Fat; Disease resistance; Eating - genetics; Energy expenditure; Energy Metabolism - genetics; Feeding Behavior; Food intake; Frizzled protein; Frizzled-related protein; Gene Knock-In Techniques; Glucose; Glucose metabolism; Glucose tolerance; Glucose Tolerance Test; HEK293 Cells; High fat diet; Homeostasis; Homeostasis - genetics; Humans; Insulin; Insulin - metabolism; Insulin resistance; Insulin secretion; Insulin-Secreting Cells - metabolism; Male; Males; Mice; Mice, Knockout; Obesity; Proto-Oncogene Proteins - genetics; Spine; Wnt protein; Wnt Signaling Pathway; X-Ray Microtomography
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2015-1257

Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway. SFRP4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. However, the exact role of SFRP4 in regulating whole-body metabolism and glucose homeostasis is unknown. We show here that male Sfrp4−/− mice have increased spine length and gain more weight when fed a high-fat diet. The body composition and body mass per spine length of diet-induced obese Sfrp4−/− mice is similar to wild-type littermates, suggesting that the increase in body weight can be accounted for by their longer body size. The diet-induced obese Sfrp4−/− mice have reduced energy expenditure, food intake, and bone mineral density. Sfrp4−/− mice have normal glucose and insulin tolerance and β-cell mass. Diet-induced obese Sfrp4−/− and control mice show similar impairments of glucose tolerance and a 5-fold compensatory expansion of their β-cell mass. In summary, our data suggest that loss of SFRP4 alters body length and bone mineral density as well as energy expenditure and food intake. However, SFRP4 does not control glucose homeostasis and β-cell mass in mice.