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TRPC6 deficiency causes obesity and metabolic dysfunction
Author(s) -
Bailey Kandice,
Wang Zhen,
Moak Sydney P.,
Dai Xuemei,
Fu Yiling,
Carmo Jussara M.,
Silva Alexandre A.,
Hall John E.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.753.1
Subject(s) - trpc , endocrinology , medicine , leptin , lean body mass , trpc6 , obesity , heart rate , metabolic syndrome , biology , blood pressure , chemistry , transient receptor potential channel , receptor , body weight
Transient receptor potential cation channel C (TRPC) is a group of receptor‐operated cation channels that modulate cell Ca 2+ influx. TPRC6 is a subunit of the TRPC family that is expressed in the brain. However, the role of TRPC6 in controlling metabolic and cardiovascular functions remains unknown. In this study, we investigated the impact of genetic TRPC6 deletion on energy balance, metabolic and cardiovascular functions, and anorexic responses to leptin. Metabolic phenotypes including body weight (BW), food intake (FI), body fat/lean composition, energy expenditure (EE), respiratory quotient (RQ), responses to acute leptin injection as well as cardiovascular parameters including blood pressure (BP) and heart rate (HR) were measured by telemetry in male and female TRPC6 null and B6/129 control mice (n=7/per group and sex). TRPC6 null mice were heavier than control mice from 6 to 16 weeks of age when fed a standard diet (39.5±1.5 vs 31.1±1.2 g in males and 31.1±1.2 vs 22.9±1.0 g in females at 16 weeks of age, p <0.05). EchoMRI scans showed that the higher BW of TRPC6 null mice was mainly due to increased body fat compared to controls (30.0 vs 22.6 % of fat mass/BW in males and 32.7 vs 21.0 % in females at 16 weeks of age), and was associated with increased FI (3.4±0.1 vs 2.7±0.2 g/day in males and 2.7±0.1 vs 2.0±0.1 g/day in females at 16 weeks of age, p <0.05). EE, assessed by indirect calorimetry, was significantly reduced in TRPC6 null mice (0.108±0.003 vs 0.205±0.012 kcal/12h/g in males and 0.178±0.005 vs 0.217±0.006 kcal/12h/g in females at 17 weeks of age, p <0.05) and was accompanied by significantly reduced 24‐h average RQ (0.80±0.01 vs 0.89±0.01 in males and 0.77±0.01 vs 0.84± 0.01 in females at 17 weeks of age, p <0.05) when compared to male and female controls. Acute leptin injections (5 mg/kg, i.p. at 18 weeks of age) reduced 24‐hr FI by 41% and 32 % in male and female control mice, respectively, while only 8 % and 18 % reductions in FI were observed in male and female TRPC6 null mice. BP and HR measured by telemetry for 5 consecutive days at 22 weeks of age were similar in TRPC6 null mice and control mice (MAP: 111±2 vs 108±2 in males and 103±3 vs 108±3 in females; HR: 541±9 vs 526±14 in males and 552±4 vs 552±27 in females). Our results indicate that TRPC6 plays an important role in normal control of FI, BW and energy balance as well as for normal anorexic responses to leptin. Although TRPC6 deficiency caused obesity and metabolic abnormalities, BP and HR did not increase suggesting that TRPC6 may be an important link between obesity and hypertension. Support or Funding Information NHLBI PO1HL51971, NIGMS P20GM104357 and U54GM115428, and NIDDK R00DK113280 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .