Sex differences in the metabolic dysfunction and insulin resistance of skeletal muscle glucose transport following high fructose ingestion

Abstract

The role of high fructose ingestion (HFI) in the development of conditions mimicking human metabolic syndrome has mostly been demonstrated in male animals; however, the extent of HFI-induced metabolic alterations in females remains unclear. The present study investigated whether HFI-induced metabolic perturbations differ between sexes and whether HFI aggravates the metabolic disturbances under ovarian hormone deprivation. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) for 6 wk. Blood pressure, glucose tolerance, insulin-stimulated glucose transport activity and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, JNK, p38 MAPK, angiotensin-converting enzyme (ACE), ANG II type 1 receptor (ATR), ACE2, and Mas receptor (MasR) in skeletal muscle, were evaluated. We found that HFI led to glucose intolerance and hypertension in male and OVX rats but not in female rats with intact ovaries. Moreover, HFI did not induce insulin resistance in the skeletal muscle of female and OVX rats but impaired the insulin-stimulated glucose transport activity in the skeletal muscle of male rats, which was accompanied by lower insulin-stimulated IRS-1 Tyr (44%), Akt Ser (30%), and AS160 Ser (43%), and increases in insulin-stimulated IRS-1 Ser (78%), JNK Thr/Tyr (69%), and p38 MAPK Thr/Tyr (81%). The results from the present study show sex differences in the development of metabolic syndrome-like conditions and indicate the protective role of female sex hormones against HFI-induced cardiometabolic abnormalities.

Recent Developments in Rodent Models of High-Fructose Diet-Induced Metabolic Syndrome: A Systematic Review

“…In such studies, there is notable inter- and intra-species variation in the outcome between mice ( Mus musculus ) and rats ( Rattus norvegicus ). Among rats, the most reliable strains are Sprague–Dawley (SD) rats and spontaneously hypertensive rats (SHR) [ 33 , 34 , 35 , 36 , 38 , 39 , 40 , 41 , 43 , 46 ]. Both strains can manifest the many characteristics of MetS with no serious inconsistencies or conflicts.…”

Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver

“…Male (n ϭ 12), female (n ϭ 12), and ovariectomized (OVX, n ϭ 12) rats were randomly assigned to receive either control diet (TD08806, 10% kcal as fat; Envigo (formerly Harlan-Teklad; Cambridgeshire, UK) with reverse osmosis water or a high-fat diet (TD06414, 60% kcal as fat; Envigo) with 30% wt/vol fructose in drinking water for 12 wk ad libitum. Ovariectomy was conducted according to the procedure described previously (26), and animals were allowed to recover for 7 days following surgery. Body weight as well as food and water intake were assessed three times a week throughout the 12 wk of feeding.…”

Estrogen and voluntary exercise attenuate cardiometabolic syndrome and hepatic steatosis in ovariectomized rats fed a high-fat high-fructose diet

“…Animals were randomly assigned to either sham operation (SHAM, n ϭ 8) or bilateral ovariectomy (OVX, n ϭ 29). Surgical procedures were performed under anesthesia through bilateral skin incisions at the lower back, as previously described (45). SHAM rats were fed a control diet [TD08806, 10% kcal as fat; Envigo (formerly Harlan Teklad), Cambridgeshire, UK] with reverse osmosis water.…”