Effect of Cold Exposure and Exercise on Insulin Sensitivity and Serum Free Fatty Acids in Obese Rats

Abstract

PurposeThis study aimed to explore the effect of exercise and cold exposure on insulin sensitivity and the level of serum free fatty acids (FFA) in diet-induced obese rats.MethodsSixty-four diet-induced obese rats were randomly assigned to eight groups: room temperature–sedentary, room temperature–exercise, acute cold exposure–sedentary, acute cold exposure–exercise, intermittent cold exposure–sedentary, intermittent cold exposure–exercise, sustained cold exposure–sedentary, and sustained cold exposure–exercise. After the interventions, the homeostatic model assessment for insulin resistance (HOMA-IR) values, the level of serum FFA, subcutaneous fat ratio (SFR) and visceral fat ratio, enzyme activities of adipose triglyceride lipase, and lipoprotein lipase (LPL) in inguinal adipose tissue, and protein expression of PGC1-α and p38 MAPK in skeletal muscle were investigated.ResultsWe found that exercise (P = 0.0136) and cold exposure (P < 0.0001) reduced HOMA-IR values independently. Exercise reduced serum FFA (P = 0.0041), whereas cold exposure did not affect them. Moreover, the HOMA-IR values were positively correlated with the serum FFA levels (r = 0.32, P = 0.01). SFR or visceral fat ratio was coordinately reduced by the interaction (for SFR, P = 0.0015) or opposing main effects between or of cold exposure and exercise, supporting the reduction of serum FFA. However, cold exposure or exercise increased the activity of adipose triglyceride lipase and LPL independently or interactively (for LPL, P = 0.0143), suggesting an increase in serum FFA. Finally, cold exposure and exercise enhanced protein expression of PGC1-α and p38 MAPK independently or interactively (for p38 MAPK, P = 0.0226), suggesting increased uptake and oxidation of serum FFA in muscle.ConclusionsThese results suggest that the combination of exercise and cold exposure may result in more serum FFA utilization than production and thus lead to reduced serum FFA and increased insulin sensitivity.

The Effects of Intermittent Cold Exposure on Adipose Tissue

“…Here, and in Table 2, we outline the effects of ICE on body weight (BW), adipose tissue weight (white adipose tissue (WAT) and brown adipose tissue (BAT), adipose tissue morphology (WAT and BAT), EE, and outcomes that may be related to EE. Winter swimmers: higher supraclavicular skin temp in response to cold exposure, no BAT glucose uptake at thermoneutrality (controls had glucose uptake at thermoneutrality), ↑glucose uptake in perirenal BAT during cold exposure (not significant for control), ↑REE during cold exposure Humans Zhang [37] ↓BW, ↑EI (trend) Rats McKie [38] ↑BW, ↑iWAT, ↑eWAT, ↑BAT, ↑EI, ↑↑EI (within 4 h post ICE) Obese Mice Weng [39] ↑sWAT, ↔vWAT Obese Rats Nema [9] ↔BW, ↔BMI, ↔FM, ↔FFM, ↓Waist Circumference (men only) Humans (Soldiers)…”

“…Obese Mice Caloric Restriction During ICE 24 h ad libitum after ICE Zhang [37] ↑peri-ovarian adipose thermogenic gene expression (Ucp1, PGC1α, Prdm16, Fndc5) Rats Weng [39] ↔iWAT ATGL activity, ↑iWAT LPL activity Obese Rats…”

“…In Table 4, we summarize the reports for ICE-induced changes in these systemic factors and discuss them below. ↓BG, ↓cortisol Humans Wang [29] ↑glucose tolerance, ↑insulin sensitivity Mice Bai [30] ↔serum glucose, ↔serum TG Platue Pika (Rodent) Hanssen [31] ↑IS, ↑GLUT4 translocation in skeletal muscle Humans (Overweight,T2D, Males) Gibas-Dorna [32] ↑IS during the portion of the winter swimming season where water temperature was <8 • C Humans Hanssen [34] ↑skeletal muscle glucose uptake during ICE, ↑GLUT4 translocation in skeletal muscle Humans (Obese) Blondin [35] ↔FG Humans Soberg [16] winter swimmers had ↓plasma glucose during IGTT Humans McKie [38] ↑glucose tolerance, ↑insulin and c-peptide in response to glucose, ↔IS Obese Mice Weng [39] ↔BG, ↔insulin, ↓HOMA-IR, ↔FFA Obese Rats…”

“…Despite the lacking evidence for ICE to modulate BW, there is some evidence for its impact on white adipose tissue (WAT) weight and implications for WAT function based on morphology. Generally, ICE tends to increase the subcutaneous WAT (sWAT) [ 25 , 32 , 38 , 39 ] and has variable effects on the visceral WAT (vWAT), where increases [ 25 , 27 , 30 , 38 ], decreases [ 20 , 23 , 24 , 29 , 32 ], and null effects [ 36 , 39 ] are reported. In humans, winter swimmers have an increased fat mass, but a decrease in vWAT as estimated via electrical impedance [ 32 ].…”

“…Although direct evidence of a linkage between ICE and the modulation of adipokines, such as leptin and adiponectin, is fairly limited, some studies have demonstrated favorable alterations in glucose homeostasis and insulin sensitivity associated with changes in adipose tissue biochemical factors. Weng et al reported that a combination of ICE and exercise in rats resulted in several effects on free fatty acid (FFA) production and utilization, producing the net effect of reducing insulin resistance, HOMA-IR, and blood glucose, with a main effect of ICE independent of exercise [ 39 ]. This study further demonstrated that adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL) activity in inguinal adipose tissue were increased in response to ICE and that the skeletal muscle FFA oxidative capacity elevated via increases in PPARG coactivator 1 alpha (PGC-1α) and p38 mitogen-activated protein kinases (p38MAPK) in response to ICE, thereby offsetting the increases in FFA delivered to the circulation via increased lipolysis.…”